Skip to content
2000
image of New Drug Therapies Targeting Neurodegenerative Diseases: A Comprehensive Review

Abstract

Neurodegenerative diseases encompass well-characterized behavioral, cognitive, and movement disorders that affect older people, impacting all facets of daily life. In Alzheimer's disease, specific antibodies targeting the β-amyloid protein (aducanumab, lecanemab, and others) are gaining special interest due to the approval of the first particular drugs against this disease. In Parkinson's disease, most drugs were approved several decades ago; however, new Phase II clinical trials point to monoclonal antibodies as a promising approach, and the report of alkaloids also suggests various therapeutic targets against this disease. Pick’s disease has a low prevalence; currently, no drugs are approved by government agencies. However, thanks to molecular tools, it has been possible to elucidate therapeutic targets implicated in the appearance of the disease. α-synuclein is the main therapeutic target in Lewy body disease; most of the reported molecules are in clinical Phases I and II. Additionally, drug repositioning may emerge as a viable option in the search for effective treatments against this disease. In amyotrophic lateral sclerosis, the appearance of newly approved drugs such as tofersen and edaravone, and some others in clinical Phase II (bosutinib), opens a new era in the understanding and treatment of this condition. Altered emotions and progressive damage in some brain regions characterize schizophrenia and vascular dementia. Combinations of tricyclic drugs are a trend that aims to increase the cognitive performance of patients with schizophrenia. In vascular dementia, numerous trials with molecules of different natures (flavonoids and lactones) have yielded positive results, delaying the progression of the disease. This review examines recent reports on molecules evaluated and models of the primary neurodegenerative diseases.

Loading

Article metrics loading...

/content/journals/cnsamc/10.2174/0118715249397580251117044621
2026-01-07
2026-02-28
Loading full text...

Full text loading...

References

  1. Sandoval-Avila S. Diaz N.F. Gómez-Pinedo U. Canales-Aguirre A.A. Gutiérrez-Mercado Y.K. Padilla-Camberos E. Marquez-Aguirre A.L. Díaz-Martínez N.E. Neuroprotective effects of phytochemicals on dopaminergic neuron cultures. Neurología (Engl. Ed) 2019 34 2 114 124 10.1016/j.nrleng.2016.04.014 27342389
    [Google Scholar]
  2. WHO guidelines for reducing the risks of cognitive decline and dementia. 2024 Available from:https://www.paho.org/es/documentos/directrices-oms-para-reduccion-riesgos-deterioro-cognitivo-demencia
  3. Dinda B. Dinda M. Kulsi G. Chakraborty A. Dinda S. Therapeutic potentials of plant iridoids in Alzheimer’s and Parkinson’s diseases: A review. Eur. J. Med. Chem. 2019 169 169 185 199 10.1016/j.ejmech.2019.03.009 30877973
    [Google Scholar]
  4. Wong W. Economic burden of Alzheimer disease and managed care considerations. Am J. Manag. Care 2020 26 8 S177 S183.(Suppl. 8) 10.37765/ajmc.2020.88482 32840331
    [Google Scholar]
  5. Prince M. Bryce R. Albanese E. Wimo A. Ribeiro W. Ferri C.P. The global prevalence of dementia: A systematic review and metaanalysis. Alzheimers Dement. 2013 9 1 63 75.e2 10.1016/j.jalz.2012.11.007 23305823
    [Google Scholar]
  6. Garre-Olmo J. Epidemiology of Alzheimer’s disease and other dementias. Rev. Neurol. 2018 66 11 377 386 29790571
    [Google Scholar]
  7. Hendriks S. Peetoom K. Bakker C. van der Flier W.M. Papma J.M. Koopmans R. Verhey F.R.J. de Vugt M. Köhler S. Withall A. Parlevliet J.L. Uysal-Bozkir Ö. Gibson R.C. Neita S.M. Nielsen T.R. Salem L.C. Nyberg J. Lopes M.A. Dominguez J.C. De Guzman M.F. Egeberg A. Radford K. Broe T. Subramaniam M. Abdin E. Bruni A.C. Di Lorenzo R. Smith K. Flicker L. Mol M.O. Basta M. Yu D. Masika G. Petersen M.S. Ruano L. Global prevalence of young-onset dementia: A systematic review and meta-analysis. JAMA Neurol. 2021 78 9 1080 1090 10.1001/jamaneurol.2021.2161 34279544
    [Google Scholar]
  8. Nandi A. Counts N. Bröker J. Malik S. Chen S. Han R. Klusty J. Seligman B. Tortorice D. Vigo D. Bloom D.E. Cost of care for Alzheimer’s disease and related dementias in the United States: 2016 to 2060. NPJ Aging 2024 10 1 13 10.1038/s41514‑024‑00136‑6 38331952
    [Google Scholar]
  9. Luo Y. Qiao L. Li M. Wen X. Zhang W. Li X. Global, regional, national epidemiology and trends of Parkinson’s disease from 1990 to 2021: findings from the Global Burden of Disease Study 2021. Front. Aging Neurosci. 2025 16 1498756 10.3389/fnagi.2024.1498756 39868382
    [Google Scholar]
  10. Wijers A. Ravi A. Evers S.M.A.A. Tissingh G. van Mastrigt G.A.P.G. Systematic review of the cost of illness of Parkinson’s disease from a societal perspective. Mov. Disord. 2024 39 11 1938 1951 10.1002/mds.29995 39221849
    [Google Scholar]
  11. Valentino R.R. Scotton W.J. Roemer S.F. Lashley T. Heckman M.G. Shoai M. Martinez-Carrasco A. Tamvaka N. Walton R.L. Baker M.C. Macpherson H.L. Real R. Soto-Beasley A.I. Mok K. Revesz T. Christopher E.A. DeTure M. Seeley W.W. Lee E.B. Frosch M.P. Molina-Porcel L. Gefen T. Redding-Ochoa J. Ghetti B. Robinson A.C. Kobylecki C. Rowe J.B. Beach T.G. Teich A.F. Keith J.L. Bodi I. Halliday G.M. Gearing M. Arzberger T. Morris C.M. White C.L. Mechawar N. Boluda S. MacKenzie I.R. McLean C. Cykowski M.D. Wang S.H.J. Graff C. Nagra R.M. Kovacs G.G. Giaccone G. Neumann M. Ang L.C. Carvalho A. Morris H.R. Rademakers R. Hardy J.A. Dickson D.W. Rohrer J.D. Ross O.A. Warner T.T. Jaunmuktane Z. Boeve B.F. Duara R. Graff-Radford N.R. Josephs K.A. Knopman D.S. Koga S. Murray M.E. Lyons K.E. Pahwa R. Petersen R.C. Whitwell J.L. Grinberg L.T. Miller B. Schlereth A. Spina S. Grossman M. Irwin D.J. Suh E.R. Trojanowski J.Q. Van Deerlin V.M. Wolk D.A. Connors T.R. Dooley P.M. Oakley D.H. Aldecoa I. Balasa M. Gelpi E. Borrego-Écija S. Gascon-Bayarri J. Sánchez-Valle R. Sanz-Cartagena P. Piñol-Ripoll G. Bigio E.H. Flanagan M.E. Rogalski E.J. Weintraub S. Schneider J.A. Peng L. Zhu X. Chang K. Troncoso J.C. Prokop S. Newell K.L. Jones M. Richardson A. Roncaroli F. Snowden J. Allinson K. Singh P. Serrano G.E. Flowers X.E. Goldman J.E. Heaps A.C. Leskinen S.P. Black S.E. Masellis M. King A. Al-Sarraj S. Troakes C. Hodges J.R. Kril J.J. Kwok J.B. Piguet O. Roeber S. Attems J. Thomas A.J. Evers B.M. Bieniek K.F. Sieben A.A. Cras P.P. De Vil B.B. Bird T. Castellani R.J. Chaffee A. Franklin E. Haroutunian V. Jacobsen M. Keene D. Latimer C.S. Metcalf J. Perrin R.J. Purohit D.P. Rissman R.A. Schantz A. Walker J. De Deyn P.P. Duyckaerts C. Le Ber I. Seilhean D. Turbant-Leclere S. Ervin J.F. Nennesmo I. Riehl J. Nacmias B. Finger E.C. Blauwendraat C. Nalls M.A. Singleton A.B. Vitale D. Cunha C. Wszolek Z.K. MAPT H2 haplotype and risk of Pick’s disease in the Pick’s disease International Consortium: A genetic association study. Lancet Neurol. 2024 23 5 487 499 10.1016/S1474‑4422(24)00083‑8 38631765
    [Google Scholar]
  12. Coyle-Gilchrist I.T.S. Dick K.M. Patterson K. Vázquez Rodríquez P. Wehmann E. Wilcox A. Lansdall C.J. Dawson K.E. Wiggins J. Mead S. Brayne C. Rowe J.B. Prevalence, characteristics, and survival of frontotemporal lobar degeneration syndromes. Neurology 2016 86 18 1736 1743 10.1212/WNL.0000000000002638 27037234
    [Google Scholar]
  13. Galvin J.E. Howard D.H. Denny S.S. Dickinson S. Tatton N. The social and economic burden of frontotemporal degeneration. Neurology 2017 89 20 2049 2056 10.1212/WNL.0000000000004614 28978658
    [Google Scholar]
  14. Desai U. Chandler J. Kirson N. Georgieva M. Cheung H.C. Westermeyer B. Lane H. Biglan K. Epidemiology and economic burden of Lewy body dementia in the United States. Curr. Med. Res. Opin. 2022 38 7 1177 1188 10.1080/03007995.2022.2059978 35442134
    [Google Scholar]
  15. Mehta P. Raymond J. Nair T. Han M. Berry J. Punjani R. Larson T. Mohidul S. Horton D.K. Amyotrophic lateral sclerosis estimated prevalence cases from 2022 to 2030, data from the national ALS Registry. Amyotroph. Lateral Scler. Frontotemporal Degener. 2025 26 3-4 290 295 10.1080/21678421.2024.2447919 39749668
    [Google Scholar]
  16. Thakore N.J. Pioro E.P. Udeh B.L. Lapin B.R. Katzan I.L. A cost-effectiveness framework for amyotrophic lateral sclerosis, applied to riluzole. Value Health 2020 23 12 1543 1551 10.1016/j.jval.2020.06.012 33248509
    [Google Scholar]
  17. Larkindale J. Yang W. Hogan P.F. Simon C.J. Zhang Y. Jain A. Habeeb-Louks E.M. Kennedy A. Cwik V.A. Cost of illness for neuromuscular diseases in the United States. Muscle Nerve 2014 49 3 431 438 10.1002/mus.23942 23836444
    [Google Scholar]
  18. Moreno-Küstner B. Martín C. Pastor L. Prevalence of psychotic disorders and its association with methodological issues. A systematic review and meta-analyses. PLoS One 2018 13 4 e0195687 10.1371/journal.pone.0195687 29649252
    [Google Scholar]
  19. Kotzeva A. Mittal D. Desai S. Judge D. Samanta K. Socioeconomic burden of schizophrenia: a targeted literature review of types of costs and associated drivers across 10 countries. J. Med. Econ. 2023 26 1 70 83 10.1080/13696998.2022.2157596 36503357
    [Google Scholar]
  20. Rizzi L. Rosset I. Roriz-Cruz M. Global epidemiology of dementia: Alzheimer’s and vascular types. BioMed Res. Int. 2014 2014 1 8 10.1155/2014/908915 25089278
    [Google Scholar]
  21. Chen Y. Wilson L. Kornak J. Dudley R.A. Merrilees J. Bonasera S.J. Byrne C.M. Lee K. Chiong W. Miller B.L. Possin K.L. The costs of dementia subtypes to California Medicare fee‐for‐service, 2015. Alzheimers Dement. 2019 15 7 899 906 10.1016/j.jalz.2019.03.015 31175026
    [Google Scholar]
  22. Lane C.A. Hardy J. Schott J.M. Alzheimer’s disease. Eur. J. Neurol. 2018 25 1 59 70 10.1111/ene.13439 28872215
    [Google Scholar]
  23. Mantzavinos V. Alexiou A. Biomarkers for Alzheimer’s disease diagnosis. Curr. Alzheimer Res. 2017 14 11 1149 1154 10.2174/1567205014666170203125942 28164766
    [Google Scholar]
  24. Soria Lopez J.A. González H.M. Léger G.C. Alzheimer’s disease. Handb. Clin. Neurol. 2019 167 231 255 10.1016/B978‑0‑12‑804766‑8.00013‑3 31753135
    [Google Scholar]
  25. Vicente-Zurdo D. Rosales-Conrado N. León-González M.E. Brunetti L. Piemontese L. Pereira-Santos A.R. Cardoso S.M. Madrid Y. Chaves S. Santos M.A. Novel rivastigmine derivatives as promising multi-target compounds for potential treatment of Alzheimer’s disease. Biomedicines 2022 10 7 1510 10.3390/biomedicines10071510 35884815
    [Google Scholar]
  26. Zhang F. Zhong R. Cheng C. Li S. Le W. New therapeutics beyond amyloid-β and tau for the treatment of Alzheimer’s disease. Acta Pharmacol. Sin. 2021 42 9 1382 1389 10.1038/s41401‑020‑00565‑5 33268824
    [Google Scholar]
  27. Whitehouse P. Gandy S. Saini V. George D.R. Larson E.B. Alexander G.C. Avorn J. Brownlee S. Camp C. Chertkow H. Fugh-Berman A. Howard R. Kesselheim A. Langa K.M. Perry G. Richard E. Schneider L. Making the case for accelerated withdrawal of aducanumab. J. Alzheimers Dis. 2022 87 3 1003 1007 10.3233/JAD‑220262 35404287
    [Google Scholar]
  28. Dal-Ré R. The European Medicines Agency rejects the authorization of aducanumab for Alzheimer’s disease. Rev. Neurol. 2022 74 6 207 208 10.33588/rn.7406.2022072 35275397
    [Google Scholar]
  29. Reish N.J. Jamshidi P. Stamm B. Flanagan M.E. Sugg E. Tang M. Donohue K.L. McCord M. Krumpelman C. Mesulam M.M. Castellani R. Chou S.H.Y. Multiple Cerebral hemorrhages in a patient receiving lecanemab and treated with t-PA for stroke. N. Engl. J. Med. 2023 388 5 478 479 10.1056/NEJMc2215148 36599061
    [Google Scholar]
  30. Zeng B.S. Tseng P.T. Liang C.S. Lecanemab in early Alzheimer’s disease. N. Engl. J. Med. 2023 388 17 1630 1632 10.1056/NEJMc2301380 37099351
    [Google Scholar]
  31. Mahase E. Lecanemab: European drug agency rejects Alzheimer’s drug amid debate over efficacy and safety. BMJ 2024 386 q1692 10.1136/bmj.q1692 39074878
    [Google Scholar]
  32. Chowdhury S. Chowdhury N.S. Novel anti-amyloid-beta (Aβ) monoclonal antibody lecanemab for Alzheimer’s disease: A systematic review. Int. J. Immunopathol. Pharmacol. 2023 37 03946320231209839 10.1177/03946320231209839 37902139
    [Google Scholar]
  33. Sims J.R. Zimmer J.A. Evans C.D. Lu M. Ardayfio P. Sparks J. Wessels A.M. Shcherbinin S. Wang H. Monkul Nery E.S. Collins E.C. Solomon P. Salloway S. Apostolova L.G. Hansson O. Ritchie C. Brooks D.A. Mintun M. Skovronsky D.M. Abreu R. Agarwal P. Aggarwal P. Agronin M. Allen A. Altamirano D. Alva G. Andersen J. Anderson A. Anderson D. Arnold J. Asada T. Aso Y. Atit V. Ayala R. Badruddoja M. Badzio-jagiello H. Bajacek M. Barton D. Bear D. Benjamin S. Bergeron R. Bhatia P. Black S. Block A. Bolouri M. Bond W. Bouthillier J. Brangman S. Brew B. Brisbin S. Brisken T. Brodtmann A. Brody M. Brosch J. Brown C. Brownstone P. Bukowczan S. Burns J. Cabrera A. Capote H. Carrasco A. Cevallos Yepez J. Chavez E. Chertkow H. Chyrchel-paszkiewicz U. Ciabarra A. Clemmons E. Cohen D. Cohen R. Cohen I. Concha M. Costell B. Crimmins D. Cruz-pagan Y. Cueli A. Cupelo R. Czarnecki M. Darby D. Dautzenberg P. De Deyn P. De La Gandara J. Deck K. Dibenedetto D. Dibuono M. Dinnerstein E. Dirican A. Dixit S. Dobryniewski J. Drake R. Drysdale P. Duara R. Duffy J. Ellenbogen A. Faradji V. Feinberg M. Feldman R. Fishman S. Flitman S. Forchetti C. Fraga I. Frank A. Frishberg B. Fujigasaki H. Fukase H. Fumero I. Furihata K. Galloway C. Gandhi R. George K. Germain M. Gitelman D. Goetsch N. Goldfarb D. Goldstein M. Goldstick L. Gonzalez Rojas Y. Goodman I. Greeley D. Griffin C. Grigsby E. Grosz D. Hafner K. Hart D. Henein S. Herskowitz B. Higashi S. Higashi Y. Ho G. Hodgson J. Hohenberg M. Hollenbeck L. Holub R. Hori T. Hort J. Ilkowski J. Ingram K.J. Isaac M. Ishikawa M. Janu L. Johnston M. Julio W. Justiz W. Kaga T. Kakigi T. Kalafer M. Kamijo M. Kaplan J. Karathanos M. Katayama S. Kaul S. Keegan A. Kerwin D. Khan U. Khan A. Kimura N. Kirk G. Klodowska G. Kowa H. Kutz C. Kwentus J. Lai R. Lall A. Lawrence M. Lee E. Leon R. Linker G. Lisewski P. Liss J. Liu C. Losk S. Lukaszyk E. Lynch J. Macfarlane S. Macsweeney J. Mannering N. Markovic O. Marks D. Masdeu J. Matsui Y. Matsuishi K. Mcallister P. Mcconnehey B. Mcelveen A. Mcgill L. Mecca A. Mega M. Mensah J. Mickielewicz A. Minaeian A. Mocherla B. Murphy C. Murphy P. Nagashima H. Nair A. Nair M. Nardandrea J. Nash M. Nasreddine Z. Nishida Y. Norton J. Nunez L. Ochiai J. Ohkubo T. Okamura Y. Okorie E. Olivera E. O’mahony J. Omidvar O. Ortiz-Cruz D. Osowa A. Papka M. Parker A. Patel P. Patel A. Patel M. Patry C. Peckham E. Pfeffer M. Pietras A. Plopper M. Porsteinsson A. Poulin Robitaille R. Prins N. Puente O. Ratajczak M. Rhee M. Ritter A. Rodriguez R. Rodriguez Ables L. Rojas J. Ross J. Royer P. Rubin J. Russell D. Rutgers S.M. Rutrick S. Sadowski M. Safirstein B. Sagisaka T. Scharre D. Schneider L. Schreiber C. Schrift M. Schulz P. Schwartz H. Schwartzbard J. Scott J. Selem L. Sethi P. Sha S. Sharlin K. Sharma S. Shiovitz T. Shiwach R. Sladek M. Sloan B. Smith A. Solomon P. Sorial E. Sosa E. Stedman M. Steen S. Stein L. Stolyar A. Stoukides J. Sudoh S. Sutton J. Syed J. Szigeti K. Tachibana H. Takahashi Y. Tateno A. Taylor J.D. Taylor K. Tcheremissine O. Thebaud A. Thein S. Thurman L. Toenjes S. Toji H. Toma M. Tran D. Trueba P. Tsujimoto M. Turner R. Uchiyama A. Ussorowska D. Vaishnavi S. Valor E. Vandersluis J. Vasquez A. Velez J. Verghese C. Vodickova-borzova K. Watson D. Weidman D. Weisman D. White A. Willingham K. Winkel I. Winner P. Winston J. Wolff A. Yagi H. Yamamoto H. Yathiraj S. Yoshiyama Y. Zboch M. Donanemab in early symptomatic Alzheimer disease: the TRAILBLAZER-ALZ 2 randomized clinical trial. JAMA 2023 330 6 512 527 10.1001/jama.2023.13239 37459141
    [Google Scholar]
  34. Lowe S.L. Willis B.A. Hawdon A. Natanegara F. Chua L. Foster J. Shcherbinin S. Ardayfio P. Sims J.R. Donanemab (LY3002813) dose‐escalation study in Alzheimer’s disease. Alzheimers Dement. (N. Y.) 2021 7 1 e12112 10.1002/trc2.12112 33614890
    [Google Scholar]
  35. Bateman R.J. Cummings J. Schobel S. Salloway S. Vellas B. Boada M. Black S.E. Blennow K. Fontoura P. Klein G. Assunção S.S. Smith J. Doody R.S. Gantenerumab: an anti-amyloid monoclonal antibody with potential disease-modifying effects in early Alzheimer’s disease. Alzheimers Res. Ther. 2022 14 1 178 10.1186/s13195‑022‑01110‑8 36447240
    [Google Scholar]
  36. Karch C.M. Goate A.M. Alzheimer’s disease risk genes and mechanisms of disease pathogenesis. Biol. Psychiatry 2015 77 1 43 51 10.1016/j.biopsych.2014.05.006 24951455
    [Google Scholar]
  37. Lee C.Y.D. Daggett A. Gu X. Jiang L.L. Langfelder P. Li X. Wang N. Zhao Y. Park C.S. Cooper Y. Ferando I. Mody I. Coppola G. Xu H. Yang X.W. Elevated TREM2 gene dosage reprograms microglia responsivity and ameliorates pathological phenotypes in Alzheimer’s disease Models. Neuron 2018 97 5 1032 1048.e5 10.1016/j.neuron.2018.02.002 29518357
    [Google Scholar]
  38. Wang S. Mustafa M. Yuede C.M. Salazar S.V. Kong P. Long H. Ward M. Siddiqui O. Paul R. Gilfillan S. Ibrahim A. Rhinn H. Tassi I. Rosenthal A. Schwabe T. Colonna M. Anti-human TREM2 induces microglia proliferation and reduces pathology in an Alzheimer’s disease model. J. Exp. Med. 2020 217 9 e20200785 10.1084/jem.20200785 32579671
    [Google Scholar]
  39. Lui A. Vanleuven J. Perekopskiy D. Liu D. Xu D. Alzayat O. Elgokhy T. Do T. Gann M. Martin R. Liu D.Z. FDA-Approved kinase inhibitors in preclinical and clinical trials for neurological disorders. Pharmaceuticals 2022 15 12 1546 10.3390/ph15121546 36558997
    [Google Scholar]
  40. Viña J. Escudero J. Baquero M. Cebrián M. Carbonell-Asíns J.A. Muñoz J.E. Satorres E. Meléndez J.C. Ferrer-Rebolleda J. Cózar-Santiago M.P. Santabárbara-Gómez J.M. Jové M. Pamplona R. Tarazona-Santabalbina F.J. Borrás C. Genistein effect on cognition in prodromal Alzheimer’s disease patients. The GENIAL clinical trial. Alzheimers Res. Ther. 2022 14 1 164 10.1186/s13195‑022‑01097‑2 36329553
    [Google Scholar]
  41. Li Y. Jin Y. Wang X. Chen X. Chen H. Xu J. Duan L. Wang Y. Luo X. Wang Q. Wu Z. Neuroprotective effect of Fructus broussonetiae on APP/PS1 mice via upregulation of AKT/β-catenin signaling. Chin. J. Integr. Med. 2021 27 2 115 124 10.1007/s11655‑019‑3178‑4 31903532
    [Google Scholar]
  42. Moir R.D. Lathe R. Tanzi R.E. The antimicrobial protection hypothesis of Alzheimer’s disease. Alzheimers Dement. 2018 14 12 1602 1614 10.1016/j.jalz.2018.06.3040 30314800
    [Google Scholar]
  43. Readhead B. Haure-Mirande J.V. Funk C.C. Richards M.A. Shannon P. Haroutunian V. Sano M. Liang W.S. Beckmann N.D. Price N.D. Reiman E.M. Schadt E.E. Ehrlich M.E. Gandy S. Dudley J.T. Multiscale analysis of independent Alzheimer’s cohorts finds disruption of molecular, genetic, and clinical networks by human herpesvirus. Neuron 2018 99 1 64 82.e7 10.1016/j.neuron.2018.05.023 29937276
    [Google Scholar]
  44. Linard M. Bezin J. Hucteau E. Joly P. Garrigue I. Dartigues J.F. Pariente A. Helmer C. Antiherpetic drugs: a potential way to prevent Alzheimer’s disease? Alzheimers Res. Ther. 2022 14 1 3 10.1186/s13195‑021‑00950‑0 34996520
    [Google Scholar]
  45. Linh T.T.D. Hsieh Y.C. Huang L.K. Hu C.J. Clinical trials of new drugs for vascular cognitive impairment and vascular dementia. Int. J. Mol. Sci. 2022 23 19 11067 10.3390/ijms231911067 36232368
    [Google Scholar]
  46. Xiao S. Chan P. Wang T. Hong Z. Wang S. Kuang W. He J. Pan X. Zhou Y. Ji Y. Wang L. Cheng Y. Peng Y. Ye Q. Wang X. Wu Y. Qu Q. Chen S. Li S. Chen W. Xu J. Peng D. Zhao Z. Li Y. Zhang J. Du Y. Chen W. Fan D. Yan Y. Liu X. Zhang W. Luo B. Wu W. Shen L. Liu C. Mao P. Wang Q. Zhao Q. Guo Q. Zhou Y. Li Y. Jiang L. Ren W. Ouyang Y. Wang Y. Liu S. Jia J. Zhang N. Liu Z. He R. Feng T. Lu W. Tang H. Gao P. Zhang Y. Chen L. Wang L. Yin Y. Xu Q. Xiao J. Cong L. Cheng X. Zhang H. Gao D. Xia M. Lian T. Peng G. Zhang X. Jiao B. Hu H. Chen X. Guan Y. Cui R. Huang Q. Xin X. Chen H. Ding Y. Zhang J. Feng T. Cantillon M. Chen K. Cummings J.L. Ding J. Geng M. Zhang Z. A 36-week multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 3 clinical trial of sodium oligomannate for mild-to-moderate Alzheimer’s dementia. Alzheimers Res. Ther. 2021 13 1 62 10.1186/s13195‑021‑00795‑7 33731209
    [Google Scholar]
  47. Alzheimer type dementia 2025 Available from: https://pathology.or.jp/corepicturesEN/17/c04/03.html
  48. Food and Drug Administration (FDA) grants accelerated approval for Alzheimer's drug. 2021 Available from:https://www.fda.gov/news-events/press-announcements/fda-grants-accelerated-approval-alzheimers-drug
  49. Vitek G.E. Decourt B. Sabbagh M.N. Lecanemab (BAN2401): An anti–beta-amyloid monoclonal antibody for the treatment of Alzheimer disease. Expert Opin. Investig. Drugs 2023 32 2 89 94 10.1080/13543784.2023.2178414 36749830
    [Google Scholar]
  50. Lilly's Kisunla™ (donanemab-azbt) approved by the FDA for the treatment of early symptomatic Alzheimer's disease. 2024 Available from:https://investor.lilly.com/news-releases/news-release-details/lillys-kisunlatm-donanemab-azbt-approved-fda-treatment-early
  51. Roskoski R. Properties of FDA-approved small molecule protein kinase inhibitors: A 2023 update. Pharmacol. Res. 2023 187 106552 10.1016/j.phrs.2022.106552 36403719
    [Google Scholar]
  52. Villain N. Planche V. Lilamand M. Cordonnier C. Soto-Martin M. Mollion H. Bombois S. Delrieu J. Lecanemab for early Alzheimer’s disease: Appropriate use recommendations from the French federation of memory clinics. J. Prev. Alzheimers Dis. 2025 12 4 100094 10.1016/j.tjpad.2025.100094 40011173
    [Google Scholar]
  53. Long H. Simmons A. Mayorga A. Burgess B. Nguyen T. Budda B. Rychkova A. Rhinn H. Tassi I. Ward M. Yeh F. Schwabe T. Paul R. Kenkare-Mitra S. Rosenthal A. Preclinical and first-in-human evaluation of AL002, a novel TREM2 agonistic antibody for Alzheimer’s disease. Alzheimers Res. Ther. 2024 16 1 235 10.1186/s13195‑024‑01599‑1 39444037
    [Google Scholar]
  54. Mas-Bargues C. Borrás C. Viña J. The multimodal action of genistein in Alzheimer’s and other age-related diseases. Free Radic. Biol. Med. 2022 183 127 137 10.1016/j.freeradbiomed.2022.03.021 35346775
    [Google Scholar]
  55. Long H.Z. Cheng Y. Zhou Z.W. Luo H.Y. Wen D.D. Gao L.C. PI3K/AKT Signal pathway: A target of natural products in the prevention and treatment of Alzheimer’s disease and Parkinson’s disease. Front. Pharmacol. 2021 12 648636 10.3389/fphar.2021.648636 33935751
    [Google Scholar]
  56. Hyde V.R. Zhou C. Fernandez J.R. Chatterjee K. Ramakrishna P. Lin A. Fisher G.W. Çeliker O.T. Caldwell J. Bender O. Sauer P.J. Lugo-Martinez J. Bar D.Z. D’Aiuto L. Shemesh O.A. Anti-herpetic tau preserves neurons via the cGAS-STING-TBK1 pathway in Alzheimer’s disease. Cell Rep. 2025 44 1 115109 10.1016/j.celrep.2024.115109 39753133
    [Google Scholar]
  57. Abdoulaye I.A. Guo Y.J. A review of recent advances in neuroprotective potential of 3-N-butylphthalide and its derivatives. BioMed Res. Int. 2016 2016 1 9 10.1155/2016/5012341 28053983
    [Google Scholar]
  58. Syed Y.Y. Sodium oligomannate: first approval. Drugs 2020 80 4 441 444 10.1007/s40265‑020‑01268‑1 32020555
    [Google Scholar]
  59. Murakami H. Shiraishi T. Umehara T. Omoto S. Iguchi Y. Recent advances in drug therapy for Parkinson’s disease. Intern. Med. 2023 62 1 33 42 10.2169/internalmedicine.8940‑21 35110492
    [Google Scholar]
  60. Surguchov A. Surguchev A. Synucleins: New data on misfolding, aggregation and role in diseases. Biomedicines 2022 10 12 3241 10.3390/biomedicines10123241 36551997
    [Google Scholar]
  61. Sivanandy P. Leey T.C. Xiang T.C. Ling T.C. Wey Han S.A. Semilan S.L.A. Hong P.K. Systematic review on Parkinson’s disease medications, emphasizing on three recently approved drugs to control Parkinson’s symptoms. Int. J. Environ. Res. Public Health 2021 19 1 364 10.3390/ijerph19010364 35010624
    [Google Scholar]
  62. Papapetropoulos S. Adi N. Ellul J. Argyriou A.A. Chroni E. A prospective study of familial versus sporadic Parkinson’s disease. Neurodegener. Dis. 2007 4 6 424 427 10.1159/000107702 17934325
    [Google Scholar]
  63. Elkouzi A. Vedam-Mai V. Eisinger R.S. Okun M.S. Emerging therapies in Parkinson disease — repurposed drugs and new approaches. Nat. Rev. Neurol. 2019 15 4 204 223 10.1038/s41582‑019‑0155‑7 30867588
    [Google Scholar]
  64. Carbone F. Djamshidian A. Seppi K. Poewe W. Apomorphine for Parkinson’s disease: Efficacy and safety of current and new formulations. CNS Drugs 2019 33 9 905 918 10.1007/s40263‑019‑00661‑z 31473980
    [Google Scholar]
  65. Eijsvogel P. Misra P. Concha-Marambio L. Boyd J.D. Ding S. Fedor L. Hsieh Y.T. Sun Y.S. Vroom M.M. Farris C.M. Ma Y. de Kam M.L. Radanovic I. Vissers M.F.J.M. Mirski D. Shareghi G. Shahnawaz M. Singer W. Kremer P. Groeneveld G.J. Yu H.J. Dodart J.C. Target engagement and immunogenicity of an active immunotherapeutic targeting pathological α-synuclein: A phase 1 placebo-controlled trial. Nat. Med. 2024 30 9 2631 2640 10.1038/s41591‑024‑03101‑8 38902546
    [Google Scholar]
  66. Pagano G. Taylor K.I. Anzures Cabrera J. Simuni T. Marek K. Postuma R.B. Pavese N. Stocchi F. Brockmann K. Svoboda H. Trundell D. Monnet A. Doody R. Fontoura P. Kerchner G.A. Brundin P. Nikolcheva T. Bonni A. Prasinezumab slows motor progression in rapidly progressing early-stage Parkinson’s disease. Nat. Med. 2024 30 4 1096 1103 10.1038/s41591‑024‑02886‑y 38622249
    [Google Scholar]
  67. Weihofen A. Liu Y. Arndt J.W. Huy C. Quan C. Smith B.A. Baeriswyl J.L. Cavegn N. Senn L. Su L. Marsh G. Auluck P.K. Montrasio F. Nitsch R.M. Hirst W.D. Cedarbaum J.M. Pepinsky R.B. Grimm J. Weinreb P.H. Development of an aggregate-selective, human-derived α-synuclein antibody BIIB054 that ameliorates disease phenotypes in Parkinson’s disease models. Neurobiol. Dis. 2019 124 276 288 10.1016/j.nbd.2018.10.016 30381260
    [Google Scholar]
  68. Li K. Wang M. Huang Z.H. Wang M. Sun W.Y. Kurihara H. Huang R.T. Wang R. Huang F. Liang L. Li Y.F. Duan W.J. He R.R. ALOX5 inhibition protects against dopaminergic neurons undergoing ferroptosis. Pharmacol. Res. 2023 193 106779 10.1016/j.phrs.2023.106779 37121496
    [Google Scholar]
  69. Carroll C.B. Wyse R.K.H. Simvastatin as a potential disease-modifying therapy for patients with Parkinson’s disease: Rationale for clinical trial, and current progress. J. Parkinsons Dis. 2017 7 4 545 568 10.3233/JPD‑171203 29036837
    [Google Scholar]
  70. Zakoliukina E.S. Chuchkov V.M. Sergeeva T.N. Vezheeva O.A. Sergeev V.G. Age-related differences in LPS-induced BDNF and iNOS expression in the substantia nigra in rats. Neurosci. Behav. Physiol. 2019 49 6 773 778 10.1007/s11055‑019‑00800‑5
    [Google Scholar]
  71. Tripodi G. Lombardo M. Kerav S. Aiello G. Baldelli S. Nitric oxide in Parkinson’s disease: The potential role of dietary nitrate in enhancing cognitive and motor health via the nitrate–nitrite–nitric oxide pathway. Nutrients 2025 17 3 393 10.3390/nu17030393 39940251
    [Google Scholar]
  72. Tan W. Xue-bin C. Tian Z. Xiao-wu C. Pei-pei H. Zhi-bin C. Bei-sha T. Effects of simvastatin on the expression of inducible nitric oxide synthase and brain-derived neurotrophic factor in a lipopolysaccharide-induced rat model of Parkinson disease. Int. J. Neurosci. 2016 126 3 278 286 10.3109/00207454.2015.1012758 26000813
    [Google Scholar]
  73. Atiq A. Lee H.J. Khan A. Kang M.H. Rehman I.U. Ahmad R. Tahir M. Ali J. Choe K. Park J.S. Kim M.O. Vitamin E analog trolox attenuates MPTP-induced Parkinson’s disease in mice, mitigating oxidative stress, neuroinflammation, and motor impairment. Int. J. Mol. Sci. 2023 24 12 9942 10.3390/ijms24129942 37373089
    [Google Scholar]
  74. Sterling J. Hua P. Dunaief J.L. Cui Q.N. VanderBeek B.L. Glucagon-like peptide 1 receptor agonist use is associated with reduced risk for glaucoma. Br. J. Ophthalmol. 2023 107 2 215 220 10.1136/bjophthalmol‑2021‑319232 34413054
    [Google Scholar]
  75. Chen S.D. Chuang Y.C. Lin T.K. Yang J.L. Alternative role of glucagon-like Peptide-1 receptor agonists in neurodegenerative diseases. Eur. J. Pharmacol. 2023 938 175439 10.1016/j.ejphar.2022.175439 36470445
    [Google Scholar]
  76. Ahn Y.J. Shin H.J. Jeong E.A. An H.S. Lee J.Y. Jang H.M. Kim K.E. Lee J. Shin M.C. Roh G.S. Exendin-4 pretreatment attenuates kainic acid-induced hippocampal neuronal death. Cells 2021 10 10 2527 10.3390/cells10102527 34685508
    [Google Scholar]
  77. Singh N.K. Singh A. Varshney M. Agrawal R. A research update on exendin-4 as a novel molecule against Parkinson’s disease. Curr. Mol. Med. 2023 23 9 889 900 10.2174/1566524023666230529093314 37254536
    [Google Scholar]
  78. Tuzimski T. Petruczynik A. New trends in the practical use of isoquinoline alkaloids as potential drugs applicated in infectious and non-infectious diseases. Biomed. Pharmacother. 2023 168 115704 10.1016/j.biopha.2023.115704 37862968
    [Google Scholar]
  79. Li J. Wu Y. Dong S. Yu Y. Wu Y. Xiang B. Li Q. Research progress on neuroprotective effects of isoquinoline alkaloids. Molecules 2023 28 12 4797 10.3390/molecules28124797 37375352
    [Google Scholar]
  80. Storm C.S. Kia D.A. Almramhi M.M. Bandres-Ciga S. Finan C. Noyce A.J. Kaiyrzhanov R. Middlehurst B. Tan M. Houlden H. Morris H.R. Plun-Favreau H. Holmans P. Hardy J. Trabzuni D. Quinn J. Bubb V. Mok K.Y. Kinghorn K.J. Lewis P. Schreglmann S.R. Lovering R. R’Bibo, L.; Manzoni, C.; Rizig, M.; Ryten, M.; Guelfi, S.; Escott-Price, V.; Chelban, V.; Foltynie, T.; Williams, N.; Morrison, K.E.; Clarke, C.; Harvey, K.; Jacobs, B.M.; Brice, A.; Danjou, F.; Lesage, S.; Corvol, J-C.; Martinez, M.; Schulte, C.; Brockmann, K.; Simón-Sánchez, J.; Heutink, P.; Rizzu, P.; Sharma, M.; Gasser, T.; Schneider, S.A.; Cookson, M.R.; Blauwendraat, C.; Craig, D.W.; Billingsley, K.; Makarious, M.B.; Narendra, D.P.; Faghri, F.; Gibbs, J.R.; Hernandez, D.G.; Van Keuren-Jensen, K.; Shulman, J.M.; Iwaki, H.; Leonard, H.L.; Nalls, M.A.; Robak, L.; Bras, J.; Guerreiro, R.; Lubbe, S.; Troycoco, T.; Finkbeiner, S.; Mencacci, N.E.; Lungu, C.; Singleton, A.B.; Scholz, S.W.; Reed, X.; Uitti, R.J.; Ross, O.A.; Grenn, F.P.; Moore, A.; Alcalay, R.N.; Wszolek, Z.K.; Gan-Or, Z.; Rouleau, G.A.; Krohn, L.; Mufti, K.; van Hilten, J.J.; Marinus, J.; Adarmes-Gómez, A.D.; Aguilar, M.; Alvarez, I.; Alvarez, V.; Barrero, F.J.; Yarza, J.A.B.; Bernal-Bernal, I.; Blazquez, M.; Bonilla-Toribio, M.; Botía, J.A.; Boungiorno, M.T.; Buiza-Rueda, D.; Cámara, A.; Carrillo, F.; Carrión-Claro, M.; Cerdan, D.; Clarimón, J.; Compta, Y.; Diez-Fairen, M.; Dols-Icardo, O.; Duarte, J.; Duran, R.; Escamilla-Sevilla, F.; Ezquerra, M.; Feliz, C.; Fernández, M.; Fernández-Santiago, R.; Garcia, C.; García-Ruiz, P.; Gómez-Garre, P.; Heredia, M.J.G.; Gonzalez-Aramburu, I.; Pagola, A.G.; Hoenicka, J.; Infante, J.; Jesús, S.; Jimenez-Escrig, A.; Kulisevsky, J.; Labrador-Espinosa, M.A.; Lopez-Sendon, J.L.; de Munain Arregui, A.L.; Macias, D.; Torres, I.M.; Marín, J.; Marti, M.J.; Martínez-Castrillo, J.C.; Méndez-del-Barrio, C.; González, M.M.; Mata, M.; Mínguez, A.; Mir, P.; Rezola, E.M.; Muñoz, E.; Pagonabarraga, J.; Pastor, P.; Errazquin, F.P.; Periñán-Tocino, T.; Ruiz-Martínez, J.; Ruz, C.; Rodriguez, A.S.; Sierra, M.; Suarez-Sanmartin, E.; Tabernero, C.; Tartari, J.P.; Tejera-Parrado, C.; Tolosa, E.; Valldeoriola, F.; Vargas-González, L.; Vela, L.; Vives, F.; Zimprich, A.; Pihlstrom, L.; Toft, M.; Taba, P.; Koks, S.; Hassin-Baer, S.; Majamaa, K.; Siitonen, A.; Tienari, P.; Okubadejo, N.U.; Ojo, O.O.; Shashkin, C.; Zharkinbekova, N.; Akhmetzhanov, V.; Kaishybayeva, G.; Karimova, A.; Khaibullin, T.; Lynch, T.L.; Hingorani, A.D.; Wood, N.W. Finding genetically-supported drug targets for Parkinson’s disease using Mendelian randomization of the druggable genome. Nat. Commun. 2021 12 1 7342 10.1038/s41467‑021‑26280‑1 34930919
    [Google Scholar]
  81. Trinkaus V.A. Riera-Tur I. Martínez-Sánchez A. Bäuerlein F.J.B. Guo Q. Arzberger T. Baumeister W. Dudanova I. Hipp M.S. Hartl F.U. Fernández-Busnadiego R. In situ architecture of neuronal α-Synuclein inclusions. Nat. Commun. 2021 12 1 2110 10.1038/s41467‑021‑22108‑0 33854052
    [Google Scholar]
  82. Hauser R.A. Levodopa: Past, present, and future. Eur. Neurol. 2009 62 1 1 8 10.1159/000215875 19407449
    [Google Scholar]
  83. Wang C.Y. Wang P.N. Chiu M.J. Finstad C.L. Lin F. Lynn S. Tai Y.H. De Fang X. Zhao K. Hung C.H. Tseng Y. Peng W.J. Wang J. Yu C.C. Kuo B.S. Frohna P.A. UB‐311, a novel UBITh ® amyloid β peptide vaccine for mild Alzheimer’s disease. Alzheimers Dement. (N. Y.) 2017 3 2 262 272 10.1016/j.trci.2017.03.005 29067332
    [Google Scholar]
  84. Xiao B. Tan E.K. Prasinezumab slows motor progression in Parkinsons disease: Beyond the clinical data. NPJ Parkinsons Dis. 2025 11 1 31 10.1038/s41531‑025‑00886‑4 39971932
    [Google Scholar]
  85. Kuchimanchi M. Monine M. Kandadi Muralidharan K. Woodward C. Penner N. Phase II dose selection for alpha synuclein-targeting antibody cinpanemab (BIIB054) based on target protein binding levels in the brain. CPT Pharmacometrics Syst. Pharmacol. 2020 9 9 515 522 10.1002/psp4.12538 32613752
    [Google Scholar]
  86. Chu S. Liu S. Duan W. Cheng Y. Jiang X. Zhu C. Tang K. Wang R. Xu L. Wang X. Yu X. Wu K. Wang Y. Wang M. Huang H. Zhang J. The anti-dementia drug candidate, (−)-clausenamide, improves memory impairment through its multi-target effect. Pharmacol. Ther. 2016 162 179 187 10.1016/j.pharmthera.2016.01.002 26812265
    [Google Scholar]
  87. Vuu Y.M. Kadar Shahib A. Rastegar M. The potential therapeutic application of simvastatin for brain complications and mechanisms of action. Pharmaceuticals 2023 16 7 914 10.3390/ph16070914 37513826
    [Google Scholar]
  88. Tahir M. Kang M.H. Park T.J. Ali J. Choe K. Park J.S. Kim M.O. Multifaceted neuroprotective approach of Trolox in Alzheimer’s disease mouse model: Targeting Aβ pathology, neuroinflammation, oxidative stress, and synaptic dysfunction. Front. Cell. Neurosci. 2024 18 1453038 10.3389/fncel.2024.1453038 39355174
    [Google Scholar]
  89. Kalinderi K. Papaliagkas V. Fidani L. GLP-1 Receptor agonists: A new treatment in Parkinson’s disease. Int. J. Mol. Sci. 2024 25 7 3812 10.3390/ijms25073812 38612620
    [Google Scholar]
  90. Hussain G. Rasul A. Anwar H. Aziz N. Razzaq A. Wei W. Ali M. Li J. Li X. Role of plant derived alkaloids and their mechanism in neurodegenerative disorders. Int. J. Biol. Sci. 2018 14 3 341 357 10.7150/ijbs.23247 29559851
    [Google Scholar]
  91. Rodríguez-Leyva I. Oliva-Barrios J.E. Cueli-Barcena S. Frontotemporal dementia: Revision and our point of view. Rev. Mex Neuroci 2018 19 6 20 31 10.24875/RMN.M18000011
    [Google Scholar]
  92. Choudhury P. Scharf E.L. Paolini M.A. Graff-Radford J. Alden E.C. Machulda M.M. Jones D.T. Fields J.A. Murray M.E. Graff-Radford N.R. Constantopoulos E. Reichard R.R. Knopman D.S. Duffy J.R. Dickson D.W. Parisi J.E. Josephs K.A. Petersen R.C. Boeve B.F. Pick’s disease: Clinicopathologic characterization of 21 cases. J. Neurol. 2020 267 9 2697 2704 10.1007/s00415‑020‑09927‑9 32440921
    [Google Scholar]
  93. Takeda N. Kishimoto Y. Yokota O. Pick’s disease. Adv. Exp. Med. Biol. 2012 724 300 316 10.1007/978‑1‑4614‑0653‑2_23 22411252
    [Google Scholar]
  94. Kovacs G.G. Tauopathies. Handb. Clin. Neurol. 2018 145 25 355 368 10.1016/B978‑0‑12‑802395‑2.00025‑0 28987182
    [Google Scholar]
  95. Wheeler J.M. McMillan P. Strovas T.J. Liachko N.F. Amlie-Wolf A. Kow R.L. Klein R.L. Szot P. Robinson L. Guthrie C. Saxton A. Kanaan N.M. Raskind M. Peskind E. Trojanowski J.Q. Lee V.M.Y. Wang L.S. Keene C.D. Bird T. Schellenberg G.D. Kraemer B. Activity of the poly(A) binding protein MSUT2 determines susceptibility to pathological tau in the mammalian brain. Sci. Transl. Med. 2019 11 523 eaao6545 10.1126/scitranslmed.aao6545 31852801
    [Google Scholar]
  96. Baker J.D. Uhrich R.L. Strovas T.J. Saxton A.D. Kraemer B.C. AlphaScreen identifies MSUT2 inhibitors for tauopathy-targeting therapeutic discovery. SLAS Discov. 2021 26 3 400 409 10.1177/2472555220958387 32981422
    [Google Scholar]
  97. Guthrie C.R. Greenup L. Leverenz J.B. Kraemer B.C. MSUT2 is a determinant of susceptibility to tau neurotoxicity. Hum. Mol. Genet. 2011 20 10 1989 1999 10.1093/hmg/ddr079 21355046
    [Google Scholar]
  98. Rawat P. Sehar U. Bisht J. Selman A. Culberson J. Reddy P.H. Phosphorylated tau in Alzheimer’s disease and other tauopathies. Int. J. Mol. Sci. 2022 23 21 12841 10.3390/ijms232112841 36361631
    [Google Scholar]
  99. Soeda Y. Takashima A. New insights into drug discovery targeting tau protein. Front. Mol. Neurosci. 2020 13 590896 10.3389/fnmol.2020.590896 33343298
    [Google Scholar]
  100. Miller J.H. Das V. Potential for treatment of neurodegenerative diseases with natural products or synthetic compounds that stabilize microtubules. Curr. Pharm. Des. 2020 26 35 4362 4372 10.2174/1381612826666200621171302 32564745
    [Google Scholar]
  101. Novak P. Kovacech B. Katina S. Schmidt R. Scheltens P. Kontsekova E. Ropele S. Fialova L. Kramberger M. Paulenka-Ivanovova N. Smisek M. Hanes J. Stevens E. Kovac A. Sutovsky S. Parrak V. Koson P. Prcina M. Galba J. Cente M. Hromadka T. Filipcik P. Piestansky J. Samcova M. Prenn-Gologranc C. Sivak R. Froelich L. Fresser M. Rakusa M. Harrison J. Hort J. Otto M. Tosun D. Ondrus M. Winblad B. Novak M. Zilka N. ADAMANT: A placebo-controlled randomized phase 2 study of AADvac1, an active immunotherapy against pathological tau in Alzheimer’s disease. Nat. Aging 2021 1 6 521 534 10.1038/s43587‑021‑00070‑2 37117834
    [Google Scholar]
  102. Godyń J. Jończyk J. Panek D. Malawska B. Therapeutic strategies for Alzheimer’s disease in clinical trials. Pharmacol. Rep. 2016 68 1 127 138 10.1016/j.pharep.2015.07.006 26721364
    [Google Scholar]
  103. Novak P. Kontsekova E. Zilka N. Novak M. Ten years of tau-targeted immunotherapy: The path walked and the roads ahead. Front. Neurosci. 2018 12 798 10.3389/fnins.2018.00798 30450030
    [Google Scholar]
  104. Irwin D.J. Byrne M.D. McMillan C.T. Cooper F. Arnold S.E. Lee E.B. Van Deerlin V.M. Xie S.X. Lee V.M.Y. Grossman M. Trojanowski J.Q. Semi-automated digital image analysis of Pick’s disease and TDP-43 proteinopathy. J. Histochem. Cytochem. 2016 64 1 54 66 10.1369/0022155415614303 26538548
    [Google Scholar]
  105. Baker J.D. Uhrich R.L. Strovas T.J. Saxton A.D. Kraemer B.C. Targeting pathological Tau by small molecule inhibition of the poly(A):MSUT2 RNA-protein interaction. ACS Chem. Neurosci. 2020 11 15 2277 2285 10.1021/acschemneuro.0c00214 32589834
    [Google Scholar]
  106. Novak P. Zilka N. Zilkova M. Kovacech B. Skrabana R. Ondrus M. Fialova L. Kontsekova E. Otto M. Novak M. AADvac1, an active immunotherapy for Alzheimer’s disease and non Alzheimer tauopathies: An overview of preclinical and clinical development. J. Prev. Alzheimers Dis. 2019 6 1 63 69 10.14283/jpad.2018.45 30569088
    [Google Scholar]
  107. Theunis C. Adolfsson O. Crespo-Biel N. Piorkowska K. Pihlgren M. Hickman D.T. Gafner V. Borghgraef P. Devijver H. Pfeifer A. Van Leuven F. Muhs A. Novel phospho-tau monoclonal antibody generated using a liposomal vaccine, with enhanced recognition of a conformational tauopathy epitope. J. Alzheimers Dis. 2017 56 2 585 599 10.3233/JAD‑160695 28035925
    [Google Scholar]
  108. Rojo-Sebastián A. Ayuso-Peralta L. García-Soldevilla M.A. González-Robles C. Other degenerative dementias. Dementia with Lewy bodies, dementia in Parkinson’s disease, frontotemporal dementia and vascular dementia. Med. Program. Form Méd Cont Acred 2019 12 74 4347 4356 10.1016/j.med.2019.03.013
    [Google Scholar]
  109. Maltête D. Wallon D. Bourilhon J. Lefaucheur R. Danaila T. Thobois S. Defebvre L. Dujardin K. Houeto J.L. Godefroy O. Krystkowiak P. Martinaud O. Gillibert A. Chastan M. Vera P. Hannequin D. Welter M.L. Derrey S. Nucleus basalis of Meynert stimulation for Lewy body dementia: A phase I randomized clinical trial. Neurology 2021 96 5 e684 e697 10.1212/WNL.0000000000011227 33199437
    [Google Scholar]
  110. Svensson K.A. Hao J. Bruns R.F. Positive allosteric modulators of the dopamine D1 receptor: A new mechanism for the treatment of neuropsychiatric disorders. Adv. Pharmacol. 2019 86 273 305 10.1016/bs.apha.2019.06.001 31378255
    [Google Scholar]
  111. Biglan K. Munsie L. Svensson K.A. Ardayfio P. Pugh M. Sims J. Brys M. Safety and efficacy of mevidalen in Lewy body dementia: A phase 2, randomized, placebo-controlled trial. Mov. Disord. 2022 37 3 513 524 10.1002/mds.28879 34859493
    [Google Scholar]
  112. Odawara T. Hasegawa K. Kajiwara R. Takeuchi H. Tagawa M. Kosaka K. Murata M. Long-term efficacy and safety of zonisamide for treatment of Parkinsonism in patients with dementia with Lewy bodies: An open-label extension of a phase three randomized controlled trial. Am. J. Geriatr. Psychiatry 2022 30 3 314 328 10.1016/j.jagp.2021.07.002 34420834
    [Google Scholar]
  113. Stefani A. Santamaria J. Iranzo A. Hackner H. Schenck C.H. Högl B. Nelotanserin as symptomatic treatment for rapid eye movement sleep behavior disorder: A double-blind randomized study using video analysis in patients with dementia with Lewy bodies or Parkinson’s disease dementia. Sleep Med. 2021 81 180 187 10.1016/j.sleep.2021.02.038 33714847
    [Google Scholar]
  114. Alam J. Blackburn K. Patrick D. Neflamapimod: Clinical phase 2b-ready oral small molecule inhibitor of p38α to reverse synaptic dysfunction in early Alzheimer’s disease. J. Prev. Alzheimers Dis. 2017 4 4 273 278 10.14283/jpad.2017.41 29181493
    [Google Scholar]
  115. Jiang Y. Alam J.J. Gomperts S.N. Maruff P. Lemstra A.W. Germann U.A. Stavrides P.H. Darji S. Malampati S. Peddy J. Bleiwas C. Pawlik M. Pensalfini A. Yang D.S. Subbanna S. Basavarajappa B.S. Smiley J.F. Gardner A. Blackburn K. Chu H.M. Prins N.D. Teunissen C.E. Harrison J.E. Scheltens P. Nixon R.A. Preclinical and randomized clinical evaluation of the p38α kinase inhibitor neflamapimod for basal forebrain cholinergic degeneration. Nat. Commun. 2022 13 1 5308 10.1038/s41467‑022‑32944‑3 36130946
    [Google Scholar]
  116. Marschallinger J. Altendorfer B. Rockenstein E. Holztrattner M. Garnweidner-Raith J. Pillichshammer N. Leister I. Hutter-Paier B. Strempfl K. Unger M.S. Chishty M. Felder T. Johnson M. Attems J. Masliah E. Aigner L. The Leukotriene receptor antagonist montelukast reduces alpha-synuclein load and restores memory in an animal model of dementia with Lewy bodies. Neurotherapeutics 2020 17 3 1061 1074 10.1007/s13311‑020‑00836‑3 32072462
    [Google Scholar]
  117. Koga S. Sekiya H. Kondru N. Ross O.A. Dickson D.W. Neuropathology and molecular diagnosis of Synucleinopathies. Mol. Neurodegener. 2021 16 1 83 10.1186/s13024‑021‑00501‑z 34922583
    [Google Scholar]
  118. Wilbraham D. Biglan K.M. Svensson K.A. Tsai M. Kielbasa W. Safety, tolerability, and pharmacokinetics of mevidalen (LY3154207), a centrally acting dopamine D1 receptor-positive allosteric modulator (D1PAM), in healthy subjects. Clin. Pharmacol. Drug Dev. 2021 10 4 393 403 10.1002/cpdd.874 33029934
    [Google Scholar]
  119. Wen W. Ramaswamy S. Piscitelli S. Friedhoff L. Examining the clinical profile of nelotanserin, a novel agent in development for Lewy body dementia. Am. J. Geriatr. Psychiatry 2017 25 3 S129 S130 10.1016/j.jagp.2017.01.148
    [Google Scholar]
  120. Germann U.A. Alam J.J. P38α MAPK signaling-a robust therapeutic target for Rab5-mediated neurodegenerative disease. Int. J. Mol. Sci. 2020 21 15 5485 10.3390/ijms21155485 32751991
    [Google Scholar]
  121. Tousi B. Leverenz J.J.B. The Application of zonisamide to patients suffering from dementia with Lewy bodies: emerging clinical data. Drug Des. Devel. Ther. 2021 15 1811 1817 10.2147/DDDT.S240865 33976533
    [Google Scholar]
  122. Xiong L.Y. Ouk M. Wu C.Y. Rabin J.S. Lanctôt K.L. Herrmann N. Black S.E. Edwards J.D. Swardfager W. Leukotriene receptor antagonist use and cognitive decline in normal cognition, mild cognitive impairment, and Alzheimer’s dementia. Alzheimers Res. Ther. 2021 13 1 147 10.1186/s13195‑021‑00892‑7 34479635
    [Google Scholar]
  123. Maskovic J. Ilic A. Zugic V. Stevic Z. Stjepanovic M.I. What is the right moment for noninvasive ventilation in amyotrophic lateral sclerosis? Arch. Med. Sci. 2023 19 2 337 342 10.5114/aoms.2019.90465 37034525
    [Google Scholar]
  124. Rekatsina M. Paladini A. Piroli A. Zis P. Pergolizzi J.V. Varrassi G. Pathophysiology and therapeutic perspectives of oxidative stress and neurodegenerative diseases: A narrative review. Adv. Ther. 2020 37 1 113 139 10.1007/s12325‑019‑01148‑5 31782132
    [Google Scholar]
  125. Planas-Fontánez T.M. Dreyfus C.F. Saitta K.S. Reactive astrocytes as therapeutic targets for brain degenerative diseases: roles played by metabotropic glutamate receptors. Neurochem. Res. 2020 45 3 541 550 10.1007/s11064‑020‑02968‑6 31983009
    [Google Scholar]
  126. Wobst H.J. Mack K.L. Brown D.G. Brandon N.J. Shorter J. The clinical trial landscape in amyotrophic lateral sclerosis—Past, present, and future. Med. Res. Rev. 2020 40 4 1352 1384 10.1002/med.21661 32043626
    [Google Scholar]
  127. Genge A. Brooks B.R. Oskarsson B. Kalin A. Ji M. Apple S. Bower L. Analysis of the US safety data for edaravone (Radicava®) from the third year after launch. Drugs R D. 2022 22 3 205 211 10.1007/s40268‑022‑00391‑6 35723868
    [Google Scholar]
  128. Ikeda K. Iwasaki Y. Edaravone, a free radical Scavenger, delayed symptomatic and pathological progression of motor neuron disease in the Wobbler mouse. PLoS One 2015 10 10 e0140316 10.1371/journal.pone.0140316 26469273
    [Google Scholar]
  129. Imamura K. Izumi Y. Nagai M. Nishiyama K. Watanabe Y. Hanajima R. Egawa N. Ayaki T. Oki R. Fujita K. Uozumi R. Morinaga A. Hirohashi T. Fujii Y. Yamamoto T. Tatebe H. Tokuda T. Takahashi N. Morita S. Takahashi R. Inoue H. Safety and tolerability of bosutinib in patients with amyotrophic lateral sclerosis (iDReAM study): A multicentre, open-label, dose-escalation phase 1 trial. EClinicalMedicine 2022 53 101707 10.1016/j.eclinm.2022.101707 36467452
    [Google Scholar]
  130. Logan A. Belli A. Di Pietro V. Tavazzi B. Lazzarino G. Mangione R. Lazzarino G. Morano I. Qureshi O. Bruce L. Barnes N.M. Nagy Z. The mechanism of action of a novel neuroprotective low molecular weight dextran sulphate: New platform therapy for neurodegenerative diseases like Amyotrophic Lateral Sclerosis. Front. Pharmacol. 2022 13 983853 10.3389/fphar.2022.983853 36110516
    [Google Scholar]
  131. Proaño B. Casani-Cubel J. Benlloch M. Rodriguez-Mateos A. Navarro-Illana E. Lajara-Romance J.M. de la Rubia Ortí J.E. Is dutasteride a therapeutic alternative for amyotrophic lateral sclerosis? Biomedicines 2022 10 9 2084 10.3390/biomedicines10092084 36140184
    [Google Scholar]
  132. Wainger B.J. Macklin E.A. Vucic S. McIlduff C.E. Paganoni S. Maragakis N.J. Bedlack R. Goyal N.A. Rutkove S.B. Lange D.J. Rivner M.H. Goutman S.A. Ladha S.S. Mauricio E.A. Baloh R.H. Simmons Z. Pothier L. Kassis S.B. La T. Hall M. Evora A. Klements D. Hurtado A. Pereira J.D. Koh J. Celnik P.A. Chaudhry V. Gable K. Juel V.C. Phielipp N. Marei A. Rosenquist P. Meehan S. Oskarsson B. Lewis R.A. Kaur D. Kiskinis E. Woolf C.J. Eggan K. Weiss M.D. Berry J.D. David W.S. Davila-Perez P. Camprodon J.A. Pascual-Leone A. Kiernan M.C. Shefner J.M. Atassi N. Cudkowicz M.E. Effect of ezogabine on cortical and spinal motor neuron excitability in amyotrophic lateral sclerosis: A randomized clinical trial. JAMA Neurol. 2021 78 2 186 196 10.1001/jamaneurol.2020.4300 33226425
    [Google Scholar]
  133. Moriyama H. Yokota T. Recent progress of antisense oligonucleotide therapy for superoxide-dismutase-1-mutated amyotrophic lateral sclerosis: Focus on tofersen. Genes 2024 15 10 1342 10.3390/genes15101342 39457466
    [Google Scholar]
  134. Ou K. Jia Q. Li D. Li S. Li X.J. Yin P. Application of antisense oligonucleotide drugs in amyotrophic lateral sclerosis and Huntington’s disease. Transl. Neurodegener. 2025 14 1 4 10.1186/s40035‑025‑00466‑9 39838446
    [Google Scholar]
  135. Boros B.D. Schoch K.M. Kreple C.J. Miller T.M. antisense oligonucleotides for the study and treatment of ALS. Neurotherapeutics 2022 19 4 1145 1158 10.1007/s13311‑022‑01247‑2 35653060
    [Google Scholar]
  136. Suzuki N. Nishiyama A. Warita H. Aoki M. Genetics of amyotrophic lateral sclerosis: Seeking therapeutic targets in the era of gene therapy. J. Hum. Genet. 2023 68 3 131 152 10.1038/s10038‑022‑01055‑8 35691950
    [Google Scholar]
  137. Stoyanov G.S. Dzhenkov D.L. Petkova L. Histomorphology of amyotrophic lateral sclerosis: an autopsy case report. Cureus 2021 13 5 e14999 10.7759/cureus.14999 34150370
    [Google Scholar]
  138. Jin J. Zhong X. ASO drug Qalsody (tofersen) targets amyotrophic lateral sclerosis. Trends Pharmacol. Sci. 2023 44 12 1043 1044 10.1016/j.tips.2023.08.008 37709589
    [Google Scholar]
  139. Saitoh Y. Takahashi Y. Riluzole for the treatment of amyotrophic lateral sclerosis. Neurodegener. Dis. Manag. 2020 10 6 343 355 10.2217/nmt‑2020‑0033 32847483
    [Google Scholar]
  140. Noto Y. Shibuya K. Vucic S. Kiernan M.C. Novel therapies in development that inhibit motor neuron hyperexcitability in amyotrophic lateral sclerosis. Expert Rev. Neurother. 2016 16 10 1147 1154 10.1080/14737175.2016.1197774 27314534
    [Google Scholar]
  141. Imamura K. Izumi Y. Egawa N. Ayaki T. Nagai M. Nishiyama K. Watanabe Y. Murakami T. Hanajima R. Kataoka H. Kiriyama T. Nanaura H. Sugie K. Hirayama T. Kano O. Nakamori M. Maruyama H. Haji S. Fujita K. Atsuta N. Tatebe H. Tokuda T. Takahashi N. Morinaga A. Tabuchi R. Oe M. Kobayashi M. Lobello K. Morita S. Sobue G. Takahashi R. Inoue H. Protocol for a phase 2 study of bosutinib for amyotrophic lateral sclerosis using real-world data: Induced pluripotent stem cell-based drug repurposing for amyotrophic lateral sclerosis medicine (iDReAM) study. BMJ Open 2024 14 10 e082142 10.1136/bmjopen‑2023‑082142 39461864
    [Google Scholar]
  142. Martinez A. Palomo Ruiz M.V. Perez D.I. Gil C. Drugs in clinical development for the treatment of amyotrophic lateral sclerosis. Expert Opin. Investig. Drugs 2017 26 4 403 414 10.1080/13543784.2017.1302426 28277881
    [Google Scholar]
  143. Martín-Ruiz J. Maset-Roig R. Caplliure-Llopis J. Villarón-Casales C. Alarcón-Jiménez J. de Bernardo N. Proaño B. Menargues-Ramírez R. Selvi-Sabater P. de la Rubia-Ortí J.E. Enhanced acute muscle activation in ALS patients following liposomal curcumin, resveratrol, and dutasteride administration. Pharmaceuticals 2025 18 4 497 10.3390/ph18040497 40283933
    [Google Scholar]
  144. Srinivasan V. Homer V. Barton D. Clutterbuck-James A. Jenkins S. Potter C. Brock K. Logan A. Smith D. Bruce L. Nagy Z. Bach S.P. A low molecular weight dextran sulphate, ILB®, for the treatment of amyotrophic lateral sclerosis (ALS): An open-label, single-arm, single-centre, phase II trial. PLoS One 2024 19 7 e0291285 10.1371/journal.pone.0291285 38990927
    [Google Scholar]
  145. Cihangir Uguz A. Demirci K. Espino J. The importance of melatonin and mitochondria interaction in mood disorders and schizophrenia: A current assessment. Curr. Med. Chem. 2016 23 20 2146 2158 10.2174/0929867323666160428105849 27121187
    [Google Scholar]
  146. Morera-Fumero A. Abreu-Gonzalez P. Role of melatonin in schizophrenia. Int. J. Mol. Sci. 2013 14 5 9037 9050 10.3390/ijms14059037 23698762
    [Google Scholar]
  147. Nucifora F.C. Woznica E. Lee B.J. Cascella N. Sawa A. Treatment resistant schizophrenia: Clinical, biological, and therapeutic perspectives. Neurobiol. Dis. 2019 131 104257 10.1016/j.nbd.2018.08.016 30170114
    [Google Scholar]
  148. Zhu M.H. Liu Z.J. Hu Q.Y. Yang J.Y. Jin Y. Zhu N. Huang Y. Shi D.H. Liu M.J. Tan H.Y. Zhao L. Lv Q.Y. Yi Z.H. Wu F.C. Li Z.Z. Amisulpride augmentation therapy improves cognitive performance and psychopathology in clozapine-resistant treatment-refractory schizophrenia: A 12-week randomized, double-blind, placebo-controlled trial. Mil. Med. Res. 2022 9 1 59 10.1186/s40779‑022‑00420‑0 36253804
    [Google Scholar]
  149. Singh A. Xanomeline and trospium: A potential fixed drug combination (FDC) for schizophrenia-a brief review of current data. Innov. Clin. Neurosci. 2022 19 10-12 43 47 36591549
    [Google Scholar]
  150. Orzelska-Górka J. Mikulska J. Wiszniewska A. Biała G. New atypical antipsychotics in the treatment of schizophrenia and depression. Int. J. Mol. Sci. 2022 23 18 10624 10.3390/ijms231810624 36142523
    [Google Scholar]
  151. Danek P.J. Daniel W.A. The atypical antipsychotic lurasidone affects brain but not liver cytochrome P450 2D (CYP2D) activity. a comparison with other novel neuroleptics and significance for drug treatment of schizophrenia. Cells 2022 11 21 3513 10.3390/cells11213513 36359909
    [Google Scholar]
  152. McKeith I.G. Dickson D.W. Lowe J. Emre M. O’Brien J.T. Feldman H. Cummings J. Duda J.E. Lippa C. Perry E.K. Aarsland D. Arai H. Ballard C.G. Boeve B. Burn D.J. Costa D. Del Ser T. Dubois B. Galasko D. Gauthier S. Goetz C.G. Gomez-Tortosa E. Halliday G. Hansen L.A. Hardy J. Iwatsubo T. Kalaria R.N. Kaufer D. Kenny R.A. Korczyn A. Kosaka K. Lee V.M.Y. Lees A. Litvan I. Londos E. Lopez O.L. Minoshima S. Mizuno Y. Molina J.A. Mukaetova-Ladinska E.B. Pasquier F. Perry R.H. Schulz J.B. Trojanowski J.Q. Yamada M. Diagnosis and management of dementia with Lewy bodies. Neurology 2005 65 12 1863 1872 10.1212/01.wnl.0000187889.17253.b1 16237129
    [Google Scholar]
  153. Zhu C. Guan X. Wang Y. Liu J. Kosten T.R. Xiu M. Wu F. Zhang X. Low-dose ziprasidone in combination with sertraline for first-episode drug-naïve patients with schizophrenia: A randomized controlled trial. Neurotherapeutics 2022 19 3 1037 1046 10.1007/s13311‑022‑01242‑7 35467271
    [Google Scholar]
  154. Pham H. Warlick H. Bermudez R. Nguyen Q. Rey J.A. Olanzapine/samidorphan: A new option for the treatment of adults with schizophrenia or bipolar I disorder. J. Pharm. Technol. 2022 38 5 304 313 10.1177/87551225221114281 36046346
    [Google Scholar]
  155. Wang X. Xiu M. Wang K. Su X. Li X. Wu F. Plasma linoelaidyl carnitine levels positively correlated with symptom improvement in olanzapine-treated first-episode drug-naïve schizophrenia. Metabolomics 2022 18 7 50 10.1007/s11306‑022‑01909‑4 35819637
    [Google Scholar]
  156. Kingwell K. Schizophrenia drug shines in phase III. Nat. Rev. Drug Discov. 2022 21 10 702 10.1038/d41573‑022‑00143‑w 36045284
    [Google Scholar]
  157. Garey L.J. Ong W.Y. Patel T.S. Kanani M. Davis A. Mortimer A.M. Barnes T.R.E. Hirsch S.R. Reduced dendritic spine density on cerebral cortical pyramidal neurons in schizophrenia. J. Neurol. Neurosurg. Psychiatry 1998 65 4 446 453 10.1136/jnnp.65.4.446 9771764
    [Google Scholar]
  158. Melatonin. London, UK EMA 2007
    [Google Scholar]
  159. Haidary H.A. Padhy R.K. Clozapine. In: StatPearls. Treasure Island StatPearls Publishing 2024
    [Google Scholar]
  160. Anagnostis S. Khehra N. Parmar M.S. Chlorpromazine. In: Reference Module in Biomedical Sciences; Elsevier, 2024 2 995 1002 10.1016/B978‑0‑12‑824315‑2.00648‑5
    [Google Scholar]
  161. McNeil S.E. Gibbons J.R. Cogburn M. Risperidone. In: StatPearls. Treasure Island StatPearls Publishing 2024
    [Google Scholar]
  162. Gupta M. Amisulpride: A useful second-generation antipsychotic omitted from the US residency training curriculum. Prim. Care Companion CNS Disord. 2021 23 6 10.4088/PCC.20br02903
    [Google Scholar]
  163. Azhar Y. Shaban K. Lurasidone. In: StatPearls. Treasure Island StatPearls Publishing 2023
    [Google Scholar]
  164. Thomas K. Saadabadi A. Olanzapine. In: StatPearls. Treasure Island StatPearls Publishing 2023
    [Google Scholar]
  165. Bouchette D. Fariba K.A. Patel P. Marwaha R. Ziprasidone. In: StatPearls. Treasure Island StatPearls Publishing 2024
    [Google Scholar]
  166. Monahan C. McCoy L. Powell J. Gums J.G. Olanzapine/samidorphan: New drug approved for treating bipolar I disorder and schizophrenia. Ann. Pharmacother. 2022 56 9 1049 1057 10.1177/10600280211070330 35040357
    [Google Scholar]
  167. Lang X. Xue M. Zang X. Wu F. Xiu M. Zhang X. Efficacy of low-dose risperidone in combination with sertraline in first-episode drug-naïve patients with schizophrenia: A randomized controlled open-label study. J. Transl. Med. 2023 21 1 432 10.1186/s12967‑023‑04272‑7 37403159
    [Google Scholar]
  168. Kaul I. Sawchak S. Correll C.U. Kakar R. Breier A. Zhu H. Miller A.C. Paul S.M. Brannan S.K. Efficacy and safety of the muscarinic receptor agonist KarXT (xanomeline–trospium) in schizophrenia (EMERGENT-2) in the USA: Results from a randomised, double-blind, placebo-controlled, flexible-dose phase 3 trial. Lancet 2024 403 10422 160 170 10.1016/S0140‑6736(23)02190‑6 38104575
    [Google Scholar]
  169. Zhao L. Liu H. Wang W. Wang Y. Xiu M. Li S. Carnitine metabolites and cognitive improvement in patients with schizophrenia treated with olanzapine: A prospective longitudinal study. Front. Pharmacol. 2023 14 1255501 10.3389/fphar.2023.1255501 37663259
    [Google Scholar]
  170. Pejčić A.V. Targeting muscarinic receptors in schizophrenia treatment: Novel antipsychotic xanomeline/trospium chloride. World J. Psychiatry 2025 15 6 105409 10.5498/wjp.v15.i6.105409 40574777
    [Google Scholar]
  171. Almeria M. Alvarez I. Molina-Seguin J. Besora S. Buongiorno M. Romero S. Casas L. Cano C. Castejon J. Arribas S. Krupinski J. Citicoline may prevent cognitive decline in patients with cerebrovascular disease. Clin. Interv. Aging 2023 18 1093 1102 10.2147/CIA.S409994 37489128
    [Google Scholar]
  172. la Fleur P. Baizhaxynova A. Reynen E. Kaunelis D. Galiyeva D. Actovegin in the management of patients after ischemic stroke: A systematic review. PLoS One 2022 17 6 e0270497 10.1371/journal.pone.0270497 35771887
    [Google Scholar]
  173. Hao Z. Liu M. Liu Z. Lu D.H. Huperzine A for vascular dementia. Cochrane Libr. 2009 2 CD007365 10.1002/14651858.CD007365.pub2 19370686
    [Google Scholar]
  174. Farooq M.U. Min J. Goshgarian C. Gorelick P.B. Pharmacotherapy for vascular cognitive impairment. CNS Drugs 2017 31 9 759 776 10.1007/s40263‑017‑0459‑3 28786085
    [Google Scholar]
  175. Yang S. Wang J. Cheng P. Chen L. Hu J. Zhu G. Ginsenoside Rg1 in neurological diseases: From bench to bedside. Acta Pharmacol. Sin. 2023 44 5 913 930 10.1038/s41401‑022‑01022‑1 36380226
    [Google Scholar]
  176. Shen F. Wang J. Gao F. Wang J. Zhu G. Ginsenoside Rg1 prevents cognitive impairment and hippocampal neuronal apoptosis in experimental vascular dementia mice by promoting GPR30 expression. Neural Plast. 2021 2021 1 11 10.1155/2021/2412220 34899899
    [Google Scholar]
  177. Arriola Apelo S.I. Lamming D.W. Rapamycin: An inhibiTOR of aging emerges from the soil of Easter island. J. Gerontol. A Biol. Sci. Med. Sci. 2016 71 7 841 849 10.1093/gerona/glw090 27208895
    [Google Scholar]
  178. Shaikh S.A. Varatharajan R. Muthuraman A. Palm oil derived tocotrienol-rich fraction attenuates vascular dementia in type 2 diabetic rats. Int. J. Mol. Sci. 2022 23 21 13531 10.3390/ijms232113531 36362316
    [Google Scholar]
  179. Lin P. Tao Y. Sun F. Jiang X. Li T. Liu X. Chen M. Jiang H. Yan F. Han Y. Cao Y. Safety, tolerability and pharmacokinetics of a Class I natural medicine with therapeutic potential for vascular dementia: Naoqingzhiming tablet. Biomed. Pharmacother. 2022 153 113425 10.1016/j.biopha.2022.113425 36076546
    [Google Scholar]
  180. Peng D. Wang Y.X. Huang T.H. Luo D. Qiao L.J. Wang Q. Guan L. Cai Y.F. Zhang S.J. Ligustilide improves cognitive impairment via regulating the SIRT1/IRE1α/XBP1s/CHOP pathway in vascular dementia rats. Oxid. Med. Cell. Longev. 2022 2022 1 6664990 10.1155/2022/6664990 36017237
    [Google Scholar]
  181. Khattulanuar F.S. Sekar M. Fuloria S. Gan S.H. Rani N.N.I.M. Ravi S. Chidambaram K. Begum M.Y. Azad A.K. Jeyabalan S. Dhiravidamani A. Thangavelu L. Lum P.T. Subramaniyan V. Wu Y.S. Sathasivam K.V. Fuloria N.K. Tilianin: a potential natural lead molecule for new drug design and development for the treatment of cardiovascular disorders. Molecules 2022 27 3 673 10.3390/molecules27030673 35163934
    [Google Scholar]
  182. Jiang H. Ashraf G.M. Liu M. Zhao K. Wang Y. Wang L. Xing J. Alghamdi B.S. Li Z. Liu R. Tilianin ameliorates cognitive dysfunction and neuronal damage in rats with vascular dementia via p-CaMKII/ERK/CREB and ox-CaMKII-dependent MAPK/NF-κB pathways. Oxid. Med. Cell. Longev. 2021 2021 1 6673967 10.1155/2021/6673967 34527176
    [Google Scholar]
  183. Zhu Y. Guo X. Li S. Wu Y. Zhu F. Qin C. Zhang Q. Yang Y. Naringenin ameliorates amyloid-β pathology and neuroinflammation in Alzheimer’s disease. Commun. Biol. 2024 7 1 912 10.1038/s42003‑024‑06615‑6 39069528
    [Google Scholar]
  184. Zhang J. Zhang Y. Liu Y. Niu X. Naringenin attenuates cognitive impairment in a rat model of vascular dementia by inhibiting hippocampal oxidative stress and inflammatory response and promoting N-methyl-D-aspartate receptor signaling pathway. Neurochem. Res. 2022 47 11 3402 3413 10.1007/s11064‑022‑03696‑9 36028734
    [Google Scholar]
  185. Vinters H.V. Zarow C. Borys E. Whitman J.D. Tung S. Ellis W.G. Zheng L. Chui H.C. Review: Vascular dementia: clinicopathologic and genetic considerations. Neuropathol. Appl. Neurobiol. 2018 44 3 247 266 10.1111/nan.12472 29380913
    [Google Scholar]
  186. Kumar A. Gupta V. Sharma S. Donepezil. In: StatPearls. Treasure Island StatPearls Publishing 2025
    [Google Scholar]
  187. Kalola U.K. Patel P. Nguyen H. Galantamine.StatPearls. Treasure Island, FL StatPearls Publishing 2025
    [Google Scholar]
  188. McShane R. Westby M.J. Roberts E. Minakaran N. Schneider L. Farrimond L.E. Maayan N. Ware J. Debarros J. Memantine for dementia. Cochrane Libr. 2019 3 3 CD003154 10.1002/14651858.CD003154.pub6 30891742
    [Google Scholar]
  189. Bermejo P.E. Dorado R. Zea-Sevilla M.A. Role of citicoline in patients with mild cognitive impairment. Neurosci. Insights 2023 18 26331055231152496 10.1177/26331055231152496 36818199
    [Google Scholar]
  190. Guekht A. Skoog I. Edmundson S. Zakharov V. Korczyn A.D. ARTEMIDA trial (a randomized trial of efficacy, 12 months international double-blind actovegin): a randomized controlled trial to assess the efficacy of actovegin in poststroke cognitive impairment. Stroke 2017 48 5 1262 1270 10.1161/STROKEAHA.116.014321 28432265
    [Google Scholar]
  191. Li J. Meng X. Li F. Liu J. Ma M. Chen W. Huperzine A combined with hyperbaric oxygen on the effect on cognitive function and serum hypoxia-inducible factor-1α Level in elderly patients with vascular dementia. Am. J. Transl. Res. 2021 13 6 6897 6904 34306441
    [Google Scholar]
  192. Wu L.R. Liu L. Xiong X.Y. Zhang Q. Wang F.X. Gong C.X. Zhong Q. Yang Y.R. Meng Z.Y. Yang Q.W. Vinpocetine alleviate cerebral ischemia/reperfusion injury by down-regulating TLR4/MyD88/NF-κB signaling. Oncotarget 2017 8 46 80315 80324 10.18632/oncotarget.20699 29113305
    [Google Scholar]
  193. Wu J. Yang Y. Wan Y. Xia J. Xu J.F. Zhang L. Liu D. Chen L. Tang F. Ao H. Peng C. New insights into the role and mechanisms of ginsenoside Rg1 in the management of Alzheimer’s disease. Biomed. Pharmacother. 2022 152 113207 10.1016/j.biopha.2022.113207 35667236
    [Google Scholar]
  194. Zheng G. Wang L. Li X. Niu X. Xu G. Lv P. Rapamycin alleviates cognitive impairment in murine vascular dementia: The enhancement of mitophagy by PI3K/AKT/mTOR axis. Tissue Cell 2021 69 101481 10.1016/j.tice.2020.101481 33383488
    [Google Scholar]
  195. Couch B.A. DeMarco G.J. Gourley S.L. Koleske A.J. Increased dendrite branching in AbetaPP/PS1 mice and elongation of dendrite arbors by fasudil administration. J. Alzheimers Dis. 2010 20 4 1003 1008 10.3233/JAD‑2010‑091114 20413901
    [Google Scholar]
  196. Qin F. Yan Y. Yang N. Hao Y. Beneficial effects of echinacoside on cognitive impairment and diabetes in type 2 diabetic db/db mice. Exp. Clin. Endocrinol. Diabetes 2024 132 8 420 430 10.1055/a‑2298‑4593 38569512
    [Google Scholar]
  197. Shen L. Tian Q. Ran Q. Gan Q. Hu Y. Du D. Qin Z. Duan X. Zhu X. Huang W. Z-ligustilide: a potential therapeutic agent for atherosclerosis complicating cerebrovascular disease. Biomolecules 2024 14 12 1623 10.3390/biom14121623 39766330
    [Google Scholar]
  198. Morgan A.E. Mc Auley M.T. Vascular dementia: From pathobiology to emerging perspectives. Ageing Res. Rev. 2024 96 102278 10.1016/j.arr.2024.102278 38513772
    [Google Scholar]
  199. Nouri Z. Fakhri S. El-Senduny F.F. Sanadgol N. Abd-ElGhani G.E. Farzaei M.H. Chen J.T. On the neuroprotective effects of naringenin: Pharmacological targets, signaling pathways, molecular mechanisms, and clinical perspective. Biomolecules 2019 9 11 690 10.3390/biom9110690 31684142
    [Google Scholar]
  200. Augustin N. Nuthakki V.K. Abdullaha M. Hassan Q.P. Gandhi S.G. Bharate S.B. Discovery of helminthosporin, an anthraquinone isolated from Rumex abyssinicus Jacq as a dual cholinesterase inhibitor. ACS Omega 2020 5 3 1616 1624 10.1021/acsomega.9b03693 32010836
    [Google Scholar]
  201. Yuan C. Shin M. Park Y. Choi B. Jang S. Lim C. Yun H.S. Lee I.S. Won S.Y. Cho K.S. Linalool alleviates Aβ42-induced neurodegeneration via suppressing ROS production and inflammation in fly and rat models of Alzheimer’s disease. Oxid. Med. Cell. Longev. 2021 2021 1 8887716 10.1155/2021/8887716 33777322
    [Google Scholar]
  202. Jongwachirachai P. Ruankham W. Apiraksattayakul S. Intharakham S. Prachayasittikul V. Suwanjang W. Prachayasittikul V. Prachayasittikul S. Phopin K. Neuroprotective properties of coriander-derived compounds on neuronal cell damage under oxidative stress-induced SH-SY5Y neuroblastoma and in silico ADMET analysis. Neurochem. Res. 2024 49 12 3308 3325 10.1007/s11064‑024‑04239‑0 39298035
    [Google Scholar]
  203. Ahmad L. Mujahid M. Mishra A. Rahman M.A. Protective role of hydroalcoholic extract of Cajanus cajan Linn leaves against memory impairment in sleep deprived experimental rats. J. Ayurveda Integr. Med. 2020 11 4 471 477 10.1016/j.jaim.2018.08.003 30661946
    [Google Scholar]
  204. Gong G. Qi B. Liang Y.T. Dong T.T.X. Wang H.Y. Tsim K.W.K. Zheng Y. Danggui Buxue Tang, an ancient Chinese herbal decoction, protects β-amyloid-induced cell death in cultured cortical neurons. BMC Complement. Altern. Med. 2019 19 1 9 10.1186/s12906‑018‑2411‑6 30621672
    [Google Scholar]
  205. Mohammadnezhad P. Valdés A. Cifuentes A. Optimization and chemical characterization of extracts obtained from Ferula persica var. latisecta aerial parts and roots and their neuroprotective evaluation. Nutrients 2024 16 23 4210 10.3390/nu16234210 39683603
    [Google Scholar]
  206. Kipkemoi DJ Ireri AM Ngugi MP Cognition enhancing potential of aqueous leaf extract of Amaranthus dubius in mice. J. Evid Based Integr Med. 2023 28 2515690X231211661 10.1177/2515690X231211661
    [Google Scholar]
  207. Husna Hasnan M.H. Sivasothy Y. Khaw K.Y. Nafiah M.A. Hazni H. Litaudon M. Wan Ruzali W.A. Liew S.Y. Awang K. N-methyl costaricine and costaricine, two potent butyrylcholinesterase inhibitors from Alseodaphne pendulifolia Gamb. Int. J. Mol. Sci. 2023 24 13 10699 10.3390/ijms241310699 37445877
    [Google Scholar]
  208. Oboh G. Atoki A.V. Ademiluyi A.O. Ogunsuyi O.B. African Jointfir (Gnetum africanum) and Editan (Lasianthera africana) leaf alkaloid extracts exert antioxidant and anticholinesterase activities in fruit fly (Drosophila melanogaster). Food Sci. Nutr. 2023 11 6 2708 2718 10.1002/fsn3.3307 37324853
    [Google Scholar]
  209. Rizou A.E.I. Nasi G.I. Paikopoulos Y. Bezantakou D.S. Vraila K.D. Spatharas P.M. Dimaki V.D. Papandreou N.C. Lamari F.N. Chondrogianni N. Iconomidou V.A. A multilevel study of eupatorin and scutellarein as anti-amyloid agents in Alzheimer’s disease. Biomedicines 2023 11 5 1357 10.3390/biomedicines11051357 37239029
    [Google Scholar]
  210. On-nom N. Thangsiri S. Inthachat W. Temviriyanukul P. Sahasakul Y. Chupeerach C. Pruesapan K. Trisonthi P. Siriwan D. Suttisansanee U. Seasonal effects on phenolic contents and in vitro health-promoting bioactivities of sacred lotus (Nelumbo nucifera). Plants 2023 12 7 1441 10.3390/plants12071441 37050065
    [Google Scholar]
  211. Zheleva-Dimitrova D. Petrova A. Zengin G. Sinan K.I. Balabanova V. Joubert O. Zidorn C. Voynikov Y. Simeonova R. Gevrenova R. Metabolite profiling and bioactivity of Cicerbita alpina (L.) Wallr. (Asteraceae, Cichorieae). Plants 2023 12 5 1009 10.3390/plants12051009 36903870
    [Google Scholar]
  212. El-Hawary S.S. Sobeh M. Badr W.K. Abdelfattah M.A.O. Ali Z.Y. El-Tantawy M.E. Rabeh M.A. Wink M. HPLC-PDA-MS/MS profiling of secondary metabolites from Opuntia ficus-indica cladode, peel and fruit pulp extracts and their antioxidant, neuroprotective effect in rats with aluminum chloride induced neurotoxicity. Saudi J. Biol. Sci. 2020 27 10 2829 2838 10.1016/j.sjbs.2020.07.003 32994743
    [Google Scholar]
  213. Kim S.K. Ko Y.H. Lee Y. Lee S.Y. Jang C.G. Antineuroinflammatory effects of 7,3′,4′-trihydroxyisoflavone in lipopolysaccharide-stimulated BV2 microglial cells through MAPK and NF-κB signaling suppression. Biomol. Ther. (Seoul) 2021 29 2 127 134 10.4062/biomolther.2020.093 32812529
    [Google Scholar]
  214. El-Kashak W.A. Essa A.F. Abdelhameed M.F. Ahmed Y.H. Abd Elkarim A.S. Elghonemy M.M. Ibrahim B.M.M. Gaara A.H. Mohamed T.K. Elshamy A.I. Unveiling the neuroprotective potential of Ipomoea carnea ethanol extract via the modulation of tau and β-secretase pathways in AlCl3-induced memory impairment in rats in relation to its phytochemical profiling. Inflammopharmacology 2025 33 4 2043 2068 10.1007/s10787‑025‑01687‑0 40072673
    [Google Scholar]
  215. Takomthong P. Waiwut P. Yenjai C. Wangboonskul J. Plekratoke K. Arsito P.N. Ballatore C. Boonyarat C. Kaempferia parviflora extract and its methoxyflavones as potential anti-Alzheimer assessing in vitro, integrated computational approach, and in vivo impact on behaviour in scopolamine-induced amnesic mice. PLoS One 2025 20 3 e0316888 10.1371/journal.pone.0316888 40063637
    [Google Scholar]
  216. Dabaghian F. Delnavazi M.R. Hariri R. Akbarzadeh T. Tayarani-Najaran Z. Shams Ardekani M.R. Sharifzadeh M. Khanavi M. Neuroprotective, and memory enhancement effects of Salvia aristata and its phenolic constituents: an in vitro, and in vivo study. BMC Complement Med. Ther. 2025 25 1 181 10.1186/s12906‑025‑04902‑1 40382650
    [Google Scholar]
  217. Sut S. Dall’Acqua S. Flores G.A. Cusumano G. Koyuncu İ. Yuksekdag O. Emiliani C. Venanzoni R. Angelini P. Selvi S. Yildiztugay E. Mollica A. Procino E. Peron G. Marinaccio L. Zengin G. Hypericum empetrifolium and H. lydium as health promoting nutraceuticals: assessing their role combining in vitro in silico and chemical approaches. Food Sci. Nutr. 2025 13 4 e70053 10.1002/fsn3.70053 40171554
    [Google Scholar]
  218. Camandola S. Plick N. Mattson M.P. Impact of coffee and cacao purine metabolites on neuroplasticity and neurodegenerative disease. Neurochem. Res. 2019 44 1 214 227 10.1007/s11064‑018‑2492‑0 29417473
    [Google Scholar]
  219. Pervin M. Unno K. Takagaki A. Isemura M. Nakamura Y. Function of green tea catechins in the brain: Epigallocatechin gallate and its metabolites. Int. J. Mol. Sci. 2019 20 15 3630 10.3390/ijms20153630 31349535
    [Google Scholar]
  220. Malar D.S. Prasanth M.I. Brimson J.M. Sharika R. Sivamaruthi B.S. Chaiyasut C. Tencomnao T. Neuroprotective properties of green tea (Camellia sinensis) in Parkinson’s disease: A review. Molecules 2020 25 17 3926 10.3390/molecules25173926 32867388
    [Google Scholar]
  221. Alghamdi A.M. Al-Abbasi F.A. AlGhamdi S.A. Fatima F. Alzarea S.I. Kazmi I. Rosinidin inhibits NF-κB/Nrf2/caspase-3 expression and restores neurotransmitter levels in rotenone-activated Parkinson’s disease. Saudi J. Biol. Sci. 2023 30 6 103656 10.1016/j.sjbs.2023.103656 37187936
    [Google Scholar]
  222. Rafeeq M. Al-Abbasi F.A. Afzal M. Moglad E. Al-Qahtani S.D. Alzrea S.I. Almalki N.A.R. Imam F. Sayyed N. Kazmi I. 6-Shogaol abrogates Parkinson’s disease in rotenone-induced rodents: Based on in silico study and inhibiting TNF-α/NF-κB/IL-1β/MAO-B. Pharmaceuticals 2024 17 10 1348 10.3390/ph17101348 39458989
    [Google Scholar]
  223. Alabi A.O. Ajayi A.M. Ben-Azu B. Bakre A.G. Umukoro S. Methyl jasmonate abrogates rotenone-induced parkinsonian-like symptoms through inhibition of oxidative stress, release of pro-inflammatory cytokines, and down-regulation of immnopositive cells of NF-κB and α-synuclein expressions in mice. Neurotoxicology 2019 74 172 183 10.1016/j.neuro.2019.07.003 31336111
    [Google Scholar]
  224. Saadullah M. Sehar A. Chauhdary Z. Siddique R. Tariq H. Asif M. Bukhari S.A. Sethi A. Anti-neuroinflammatory and neuroprotective potential of Cissus tuberosa ethanol extract in Parkinson’s disease model through the modulation of neuroinflammatory markers. PLoS One 2024 19 12 e0311140 10.1371/journal.pone.0311140 39642134
    [Google Scholar]
  225. Alharthy K.M. Althurwi H.N. Albaqami F.F. Altharawi A. Alzarea S.I. Al-Abbasi F.A. Nadeem M.S. Kazmi I. Barbigerone potentially alleviates rotenone-activated Parkinson’s disease in a rodent model by reducing oxidative stress and neuroinflammatory cytokines. ACS Omega 2023 8 5 4608 4615 10.1021/acsomega.2c05837 36777578
    [Google Scholar]
  226. Kazmi I. Al-Abbasi F.A. Almalki N.A.R. Sheikh R.A. Al-Qahtani S.D. Nadeem M.S. Beg S. Afzal M. Malvidin attenuates behavioral and inhibits the TNF-α/Caspase-3/Nrf-2 expression in rotenone-induced Parkinson’s disease in rats: insights from molecular docking. Eur. Rev. Med. Pharmacol. Sci. 2024 28 9 3330 3346 10.26355/eurrev_202405_36179 38766791
    [Google Scholar]
  227. Altharawi A. Alharthy K.M. Althurwi H.N. Albaqami F.F. Alzarea S.I. Al-Abbasi F.A. Nadeem M.S. Kazmi I. Europinidin inhibits rotenone-activated Parkinson’s disease in rodents by decreasing lipid peroxidation and inflammatory cytokines pathways. Molecules 2022 27 21 7159 10.3390/molecules27217159 36363986
    [Google Scholar]
  228. Ogawa K. Ishii A. Shindo A. Hongo K. Mizobata T. Sogon T. Kawata Y. Spearmint extract containing rosmarinic acid suppresses amyloid fibril formation of proteins associated with dementia. Nutrients 2020 12 11 3480 10.3390/nu12113480 33202830
    [Google Scholar]
  229. Rane A.R. Paithankar H. Hosur R.V. Choudhary S. Modulation of α-synuclein fibrillation by plant metabolites, daidzein, fisetin and scopoletin under physiological conditions. Int. J. Biol. Macromol. 2021 182 1278 1291 10.1016/j.ijbiomac.2021.05.071 33991558
    [Google Scholar]
  230. Raha S. Dutta D. Roy A. Pahan K. Reduction of Lewy body pathology by oral cinnamon. J. Neuroimmune Pharmacol. 2021 16 3 592 608 10.1007/s11481‑020‑09955‑2 32889602
    [Google Scholar]
  231. Rosado-Ramos R. Poças G.M. Marques D. Foito A. Sevillano M. D.; Lopes-da-Silva, M.; Gonçalves, L.G.; Menezes, R.; Ottens, M.; Stewart, D.; Ibáñez de Opakua, A.; Zweckstetter, M.; Seabra, M.C.; Mendes, C.S.; Outeiro, T.F.; Domingos, P.M.; Santos, C.N. Genipin prevents alpha-synuclein aggregation and toxicity by affecting endocytosis, metabolism and lipid storage. Nat. Commun. 2023 14 1 1918 10.1038/s41467‑023‑37561‑2 37024503
    [Google Scholar]
  232. Ghanem S.S. Fayed H.S. Zhu Q. Lu J.H. Vaikath N.N. Ponraj J. Mansour S. El-Agnaf O.M.A. Natural alkaloid compounds as inhibitors for alpha-synuclein seeded fibril formation and toxicity. Molecules 2021 26 12 3736 10.3390/molecules26123736 34205249
    [Google Scholar]
  233. Yang E.J. Protective effects of a combined herbal medicine against amyotrophic lateral sclerosis-associated inflammation and oxidative stress. Appl. Sci. (Basel) 2024 14 13 5386 10.3390/app14135386
    [Google Scholar]
  234. Cai M. Yang E.J. Hochu-Ekki-To improves motor function in an amyotrophic lateral sclerosis animal model. Nutrients 2019 11 11 2644 10.3390/nu11112644 31689925
    [Google Scholar]
  235. Yang E.J. Lee S.H. Herbal medicine extracts improve motor function by anti-inflammatory activity in hSOD1G93A animal model. Mediators Inflamm. 2025 2025 1 1999953 10.1155/mi/1999953 39981400
    [Google Scholar]
  236. Mitsumoto H. Cheung K. Oskarsson B. Andrews H.F. Jang G.E. Andrews J.A. Shah J.S. Fernandes J.A. McElhiney M. Santella R.M. Randomized double-blind personalized N-of-1 clinical trial to test the safety and potential efficacy of TJ-68 for treating muscle cramps in amyotrophic lateral sclerosis (ALS): study protocol for a TJ-68 trial. Trials 2023 24 1 449 10.1186/s13063‑023‑07424‑8 37430314
    [Google Scholar]
  237. Yang E.J. Lee S.H. Anti-inflammatory effects of Chaenomeles sinensis extract in an ALS animal model. Front. Biosci. (Landmark Ed) 2023 28 12 326 10.31083/j.fbl2812326 38179776
    [Google Scholar]
  238. Zhan Y. Huang J. Tang X. Du B. Yang B. Semen Strychni Pulveratum and vomicine alleviate neuroinflammation in amyotrophic lateral sclerosis through cGAS-STING-TBK1 pathway. J. Ethnopharmacol. 2025 336 118741 10.1016/j.jep.2024.118741 39197801
    [Google Scholar]
  239. Xiong B. Yang C. Yang X. Luo S. Li S. Chen C. He K. Nie L. Li P. Li S. Huang H. Liu J. Zhang Z. Xie Y. Zou L. Yang X. Arctigenin derivative A‐1 ameliorates motor dysfunction and pathological manifestations in SOD1 G93A transgenic mice via the AMPK/SIRT1/PGC ‐1α and AMPK/SIRT1/IL ‐1β/NF‐κB pathways. CNS Neurosci. Ther. 2024 30 6 e14692 10.1111/cns.14692 38872258
    [Google Scholar]
  240. Du X. Dong Q. Zhu J. Li L. Yu X. Liu R. Rutin ameliorates ALS pathology by reducing SOD1 aggregation and neuroinflammation in an SOD1-G93A mouse model. Int. J. Mol. Sci. 2024 25 19 10392 10.3390/ijms251910392 39408720
    [Google Scholar]
  241. Ain Q.U. Saleem U. Ahmad B. Khalid I. Pharmacological screening of silibinin for antischizophrenic activity along with its acute toxicity evaluation in experimental animals. Front. Pharmacol. 2023 14 1111915 10.3389/fphar.2023.1111915 36817163
    [Google Scholar]
  242. Khalid I. Saleem U. Ahmad B. Hawwal M.F. Mothana R.A. NMDA receptor modulation by Esculetin: Investigating behavioral, biochemical and neurochemical effects in schizophrenic mice model. Saudi Pharm. J. 2024 32 4 101994 10.1016/j.jsps.2024.101994 38405040
    [Google Scholar]
  243. Omeiza N.A. Bakre A. Ben-Azu B. Sowunmi A.A. Abdulrahim H.A. Chimezie J. Lawal S.O. Adebayo O.G. Alagbonsi A.I. Akinola O. Abolaji A.O. Aderibigbe A.O. Mechanisms underpinning Carpolobia lutea G. Don ethanol extract’s neurorestorative and antipsychotic-like activities in an NMDA receptor antagonist model of schizophrenia. J. Ethnopharmacol. 2023 301 115767 10.1016/j.jep.2022.115767 36206872
    [Google Scholar]
  244. Hajizadeh Moghaddam A. Malekzadeh Estalkhi F. Khanjani Jelodar S. Ahmed Hasan T. Farhadi-Pahnedari S. Karimian M. Neuroprotective effects of alpha-pinene against behavioral deficits in ketamine-induced mice model of schizophrenia: Focusing on oxidative stress status. IBRO Neurosci. Rep. 2024 16 182 189 10.1016/j.ibneur.2023.12.012 38318342
    [Google Scholar]
  245. Porras-Dávila S.L. Jiménez-Ferrer E. Román Ramos R. González-Cortazar M. Almanza-Pérez J.C. Herrera-Ruiz M. Herniarin, dimethylfraxetin and extracts from Tagetes lucida, in psychosis secondary to ketamine and its interaction with haloperidol. Plants 2022 11 20 2789 10.3390/plants11202789 36297813
    [Google Scholar]
  246. Ngubane N.P. Mabandla M.V. De Gama B.Z. The antipsychotic potential of Salix Mucronata on ketamine-induced rats. IBRO Neurosci. Rep. 2024 17 96 107 10.1016/j.ibneur.2024.06.003 39040636
    [Google Scholar]
  247. George M.Y. Farag N. Menze E.T. Elezaby R.S. Salem N.A. Elrahmany S.K. Adel N. ElKhatib R.M. Galal M. Assem H. Elkhouly R. Wesa M.A. Hesham N. Hossam N. Ayoub I.M. Intranasal delivery of blackberry-loaded Chitosan nanoparticles for antipsychotic potential in Ketamine-induced schizophrenia in rats. Sci. Rep. 2025 15 1 16707 10.1038/s41598‑025‑00918‑2 40368975
    [Google Scholar]
  248. Kang H.B. Kim S.H. Uhm S.H. Kim D.K. Lee N.S. Jeong Y.G. Sung N.Y. Kim D.S. Han I.J. Yoo Y.C. Han S.Y. Perilla frutescens leaf extract attenuates vascular dementia-associated memory deficits, neuronal damages, and microglial activation. Curr. Issues Mol. Biol. 2022 44 1 257 272 10.3390/cimb44010019 35723398
    [Google Scholar]
  249. Sung N.S. Uhm S.H. Kang H.B. Lee N.S. Jeong Y.G. Kim D.K. Sung N.Y. Kim D.S. Yoo Y.C. Han S.Y. Rubus fruticosus leaf extract inhibits vascular dementia-induced memory impairment and neuronal loss by attenuating neuroinflammation. Anat. Cell Biol. 2023 56 4 494 507 10.5115/acb.23.195 37743615
    [Google Scholar]
  250. Morató X. Marquié M. Tartari J.P. Lafuente A. Abdelnour C. Alegret M. Jofresa S. Buendía M. Pancho A. Aguilera N. Ibarria M. Diego S. Cuevas R. Cañada L. Calvet A. Antonio E.E.D. Pérez-Cordón A. Sanabria Á. de Rojas I. Nuñez-Llaves R. Cano A. Orellana A. Montrreal L. Cañabate P. Rosende-Roca M. Vargas L. Bojaryn U. Ricciardi M. Ariton D.M. Espinosa A. Ortega G. Muñoz N. Lleonart N. Alarcón-Martín E. Moreno M. Preckler S. Tantinya N. Ramis M. Nogales A.B. Seguer S. Martín E. Pytel V. Valero S. Gurruchaga M. Tárraga L. Ruiz A. Boada M. A randomized, open-label clinical trial in mild cognitive impairment with EGb 761 examining blood markers of inflammation and oxidative stress. Sci. Rep. 2023 13 1 5406 10.1038/s41598‑023‑32515‑6 37012306
    [Google Scholar]
  251. Sirichoat A. Dornlakorn O. Saenno R. Aranarochana A. Sritawan N. Pannangrong W. Wigmore P. Welbat J.U. Caffeic acid protects against l-methionine induced reduction in neurogenesis and cognitive impairment in a rat model. Heliyon 2024 10 5 e26919 10.1016/j.heliyon.2024.e26919 38455532
    [Google Scholar]
/content/journals/cnsamc/10.2174/0118715249397580251117044621
Loading
/content/journals/cnsamc/10.2174/0118715249397580251117044621
Loading

Data & Media loading...


  • Article Type:
    Review Article
Keywords: Alzheimer ; therapeutic ; dementia ; disease ; parkinson ; drugs
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test