f Anxiety and Depression: Triggers for Cognitive Loss, Alzheimer's Disease, and Neurodegeneration

References

1. Su L.D. Wang N. Han J. Shen Y. Group 1 metabotropic glutamate receptors in neurological and psychiatric diseases: Mechanisms and prospective. Neuroscientist 2022 28 5 453 468 10.1177/10738584211021018 34088252
   [Google Scholar]
2. Chen F. Ke Q. Wei W. Cui L. Wang Y. Apolipoprotein E and viral infection: Risks and mechanisms. Mol. Ther. Nucleic Acids 2023 33 529 542 10.1016/j.omtn.2023.07.031 37588688
   [Google Scholar]
3. Santomauro D.F. Mantilla Herrera A.M. Shadid J. Zheng P. Ashbaugh C. Pigott D.M. Abbafati C. Adolph C. Amlag J.O. Aravkin A.Y. Bang-Jensen B.L. Bertolacci G.J. Bloom S.S. Castellano R. Castro E. Chakrabarti S. Chattopadhyay J. Cogen R.M. Collins J.K. Dai X. Dangel W.J. Dapper C. Deen A. Erickson M. Ewald S.B. Flaxman A.D. Frostad J.J. Fullman N. Giles J.R. Giref A.Z. Guo G. He J. Helak M. Hulland E.N. Idrisov B. Lindstrom A. Linebarger E. Lotufo P.A. Lozano R. Magistro B. Malta D.C. Månsson J.C. Marinho F. Mokdad A.H. Monasta L. Naik P. Nomura S. O’Halloran J.K. Ostroff S.M. Pasovic M. Penberthy L. Reiner R.C. Jr Reinke G. Ribeiro A.L.P. Sholokhov A. Sorensen R.J.D. Varavikova E. Vo A.T. Walcott R. Watson S. Wiysonge C.S. Zigler B. Hay S.I. Vos T. Murray C.J.L. Whiteford H.A. Ferrari A.J. COVID-19 Mental Disorders Collaborators Global prevalence and burden of depressive and anxiety disorders in 204 countries and territories in 2020 due to the COVID-19 pandemic. Lancet 2021 398 10312 1700 1712 10.1016/S0140‑6736(21)02143‑7 34634250
   [Google Scholar]
4. Fedeli U. Barbiellini Amidei C. Avossa F. Schievano E. Kingwell E. Association of multiple‐sclerosis‐related mortality with COVID‐19 and other common infections: A multiple causes of death analysis. Eur. J. Neurol. 2023 30 9 2870 2873 10.1111/ene.15912 37306563
   [Google Scholar]
5. Maiese K. Cognitive impairment in multiple sclerosis. Bioengineering 2023 10 7 871 10.3390/bioengineering10070871 37508898
   [Google Scholar]
6. Araujo-Filho I. Menseses Rêgo A.C. Post-acute covid-19 syndrome and stroke. J. Surg. Clin. Res. 2024 15 1 44 58 10.20398/jscr.v15i1.35636
   [Google Scholar]
7. Morin C.M. Carrier J. Bastien C. Godbout R. Canadian S. Circadian N. Canadian Sleep and Circadian Network Sleep and circadian rhythm in response to the COVID-19 pandemic. Can. J. Public Health 2020 111 5 654 657 10.17269/s41997‑020‑00382‑7 32700231
   [Google Scholar]
8. Maiese K. The mechanistic target of rapamycin (mTOR): Novel considerations as an antiviral treatment. Curr. Neurovasc. Res. 2020 17 3 332 337 10.2174/18755739MTA2sMTExy 32334502
   [Google Scholar]
9. Tang J. Lu L. Yuan J. Feng L. Exercise-induced activation of SIRT1/BDNF/mTORC1 signaling pathway: A novel mechanism to reduce neuroinflammation and improve post-stroke depression. Actas Esp. Psiquiatr. 2025 53 2 366 378 10.62641/aep.v53i2.1838 40071363
   [Google Scholar]
10. Tarantini L. Möller C. Schiestl V. Sordon S. Noll-Hussong M. Wittemann M. Menzie N. Riemenschneider M. Objectifying persistent subjective cognitive impairment following COVID-19 infection: Cross-sectional data from an outpatient memory-clinic in Germany. Eur. Arch. Psychiatry Clin. Neurosci. 2025 10.1007/s00406‑025‑01978‑1 40021517
    [Google Scholar]
11. Alonso J. Liu Z. Evans-Lacko S. Sadikova E. Sampson N. Chatterji S. Abdulmalik J. Aguilar-Gaxiola S. Al-Hamzawi A. Andrade L.H. Bruffaerts R. Cardoso G. Cia A. Florescu S. de Girolamo G. Gureje O. Haro J.M. He Y. de Jonge P. Karam E.G. Kawakami N. Kovess-Masfety V. Lee S. Levinson D. Medina-Mora M.E. Navarro-Mateu F. Pennell B.E. Piazza M. Posada-Villa J. ten Have M. Zarkov Z. Kessler R.C. Thornicroft G. WHO World Mental Health Survey Collaborators Treatment gap for anxiety disorders is global: Results of the world mental health surveys in 21 countries. Depress. Anxiety 2018 35 3 195 208 10.1002/da.22711 29356216
    [Google Scholar]
12. Blundell J. Kouser M. Powell C.M. Systemic inhibition of mammalian target of rapamycin inhibits fear memory reconsolidation. Neurobiol. Learn. Mem. 2008 90 1 28 35 10.1016/j.nlm.2007.12.004 18316213
    [Google Scholar]
13. Bouayed J. Rammal H. Soulimani R. Oxidative stress and anxiety: Relationship and cellular pathways. Oxid. Med. Cell. Longev. 2009 2 2 63 67 10.4161/oxim.2.2.7944 20357926
    [Google Scholar]
14. Maiese K. High anxiety: Recognizing stress as the stressor. Oxid. Med. Cell. Longev. 2009 2 2 61 62 10.4161/oxim.2.2.8842 20357925
    [Google Scholar]
15. Rowe M.K. Wiest C. Chuang D.M. GSK-3 is a viable potential target for therapeutic intervention in bipolar disorder. Neurosci. Biobehav. Rev. 2007 31 6 920 931 10.1016/j.neubiorev.2007.03.002 17499358
    [Google Scholar]
16. Aksu I. Ates M. Baykara B. Kiray M. Sisman A.R. Buyuk E. Baykara B. Cetinkaya C. Gumus H. Uysal N. Anxiety correlates to decreased blood and prefrontal cortex IGF-1 levels in streptozotocin induced diabetes. Neurosci. Lett. 2012 531 2 176 181 10.1016/j.neulet.2012.10.045 23123774
    [Google Scholar]
17. Li X. Lin X. Zhang Z. Zhuang Z. Li Y. Luo Y. Pan Y. Luo Q. Chen X. Neurotoxicity and aggressive behavior induced by anesthetic etomidate exposure in zebrafish: Insights from multi-omics and machine learning. Aquat. Toxicol. 2025 282 107321 10.1016/j.aquatox.2025.107321 40068374
    [Google Scholar]
18. Puigoriol-Illamola D. Griñán-Ferré C. Vasilopoulou F. Leiva R. Vázquez S. Pallàs M. 11β-HSD1 inhibition by RL-118 promotes autophagy and correlates with reduced oxidative stress and inflammation, enhancing cognitive performance in SAMP8 mouse model. Mol. Neurobiol. 2018 55 12 8904 8915 10.1007/s12035‑018‑1026‑8 29611102
    [Google Scholar]
19. Bahorik A. Bobrow K. Hoang T. Yaffe K. Increased risk of dementia in older female US veterans with alcohol use disorder. Addiction 2021 116 8 2049 2055 10.1111/add.15416 33449402
    [Google Scholar]
20. Barnett J.A. Bandy M.L. Gibson D.L. Is the use of glyphosate in modern agriculture resulting in increased neuropsychiatric conditions through modulation of the gut-brain-microbiome axis? Front. Nutr. 2022 9 827384 10.3389/fnut.2022.827384 35356729
    [Google Scholar]
21. Gao K. Chen C. Ke X. Fan Q. Wang H. Li Y. Chen S. Improvements of age-related cognitive decline in mice by Lactobacillus helveticus WHH1889, a novel strain with psychobiotic properties. Nutrients 2023 15 17 3852 10.3390/nu15173852 37686884
    [Google Scholar]
22. Li Y. Duan R. Gong Z. Jing L. Zhang T. Zhang Y. Jia Y. Neurofilament light chain is a promising biomarker in alcohol dependence. Front. Psychiatry 2021 12 754969 10.3389/fpsyt.2021.754969 34867542
    [Google Scholar]
23. Amanollahi M. Jameie M. Heidari A. Rezaei N. The dialogue between neuroinflammation and adult neurogenesis: Mechanisms involved and alterations in neurological diseases. Mol. Neurobiol. 2023 60 2 923 959 10.1007/s12035‑022‑03102‑z 36383328
    [Google Scholar]
24. Çalışkan H. Önal D. Nalçacı E. Darbepoetin alpha has an anxiolytic and anti-neuroinflammatory effect in male rats. BMC Immunol. 2024 25 1 75 10.1186/s12865‑024‑00665‑5 39523336
    [Google Scholar]
25. Chen Q.Y. Zhang Y. Ma Y. Zhuo M. Inhibition of cortical synaptic transmission, behavioral nociceptive, and anxiodepressive-like responses by arecoline in adult mice. Mol. Brain 2024 17 1 39 10.1186/s13041‑024‑01106‑5 38886822
    [Google Scholar]
26. Mehra S. Ahsan A.U. Sharma M. Budhwar M. Chopra M. Gestational fisetin exerts neuroprotection by regulating mitochondria-directed canonical Wnt signaling, BBB integrity, and apoptosis in prenatal VPA-induced rodent model of autism. Mol. Neurobiol. 2024 61 7 4001 4020 10.1007/s12035‑023‑03826‑6 38048031
    [Google Scholar]
27. Nagata W. Koizumi A. Nakagawa K. Takahashi S. Gotoh M. Satoh Y. Ishizuka T. Treatment with lysophosphatidic acid prevents microglial activation and depression-like behaviours in a murine model of neuropsychiatric systemic lupus erythematosus. Clin. Exp. Immunol. 2023 212 2 81 92 10.1093/cei/uxad010 36718978
    [Google Scholar]
28. Tang B. Zeng W. Song L.L. Wang H.M. Qu L.Q. Lo H.H. Yu L. Wu A.G. Wong V.K.W. Law B.Y.K. Extracellular vesicle delivery of neferine for the attenuation of neurodegenerative disease proteins and motor deficit in an Alzheimer’s disease mouse model. Pharmaceuticals 2022 15 1 83 10.3390/ph15010083 35056140
    [Google Scholar]
29. Crossnohere N.L. Campoamor N.B. Negash R. Wood M. Studts J.L. Elsaid M.I. Donneyong M. Paskett E.D. Jonas D.E. Stover D.G. Doubeni C.A. Bridges J.F.P. Public perspectives on multi-cancer early detection: A qualitative study. Cancer Contr. 2024 31 10732748241291609 10.1177/10732748241291609 39397323
    [Google Scholar]
30. Peng X. Fan R. Xie L. Shi X. Dong K. Zhang S. Tao J. Xu W. Ma D. Chen J. Yang Y. A growing link between circadian rhythms, type 2 diabetes mellitus and Alzheimer’s disease. Int. J. Mol. Sci. 2022 23 1 504 10.3390/ijms23010504 35008933
    [Google Scholar]
31. Poddar N.K. Khan A. Fatima F. Saxena A. Ghaley G. Khan S. Association of mTOR pathway and conformational alterations in C-reactive protein in neurodegenerative diseases and infections. Cell. Mol. Neurobiol. 2023 43 8 3815 3832 10.1007/s10571‑023‑01402‑z 37665407
    [Google Scholar]
32. Chongtham A. Ramakrishnan A. Farinas M. Broekaart D.W.M. Seo J.H. Zhu C.W. Sano M. Shen L. Pereira A.C. Neocortical tau propagation is a mediator of clinical heterogeneity in Alzheimer’s disease. Mol. Psychiatry 2025 10.1038/s41380‑025‑02998‑y 40234685
    [Google Scholar]
33. Clemmensen F.K. Gramkow M.H. Simonsen A.H. Ashton N.J. Huber H. Blennow K. Zetterberg H. Waldemar G. Hasselbalch S.G. Frederiksen K.S. Short-term variability of Alzheimer’s disease plasma biomarkers in a mixed memory clinic cohort. Alzheimers Res. Ther. 2025 17 1 26 10.1186/s13195‑024‑01658‑7 39838483
    [Google Scholar]
34. Elbaz E.M. Ibrahim S.M. Rashad E. Yasin N.A.E. Ghaiad H.R. Mehana N.A. Therapeutic role of l -theanine in mitigating cognitive dysfunction and neuropathology in scopolamine-treated mice. ACS Chem. Neurosci. 2025 acschemneuro.5c00351 10.1021/acschemneuro.5c00351 40504752
    [Google Scholar]
35. Hunjan G. Aran K.R. Role of mGluR7 in Alzheimer’s disease: Pathophysiological insights and therapeutic approaches. Inflammopharmacology 2025 10.1007/s10787‑025‑01765‑3 40316832
    [Google Scholar]
36. Nazir S.S. Goel D. Vohora D. A network pharmacology-based approach to decipher the pharmacological mechanisms of Salvia officinalis in neurodegenerative disorders. Metab. Brain Dis. 2025 40 5 190 10.1007/s11011‑025‑01599‑6 40266402
    [Google Scholar]
37. Zhang C. Hu Y. Cao X. Deng Y. Wang Y. Guan M. Wu X. Jiang H. Lower water-soluble vitamins and higher homocysteine are associated with neurodegenerative diseases. Sci. Rep. 2025 15 1 18866 10.1038/s41598‑025‑03859‑y 40442330
    [Google Scholar]
38. Maiese K. Biological gases, oxidative stress, artificial intelligence, and machine learning for neurodegeneration and metabolic disorders. Med. Gas Res. 2025 15 1 145 147 10.4103/mgr.MEDGASRES‑D‑24‑00059 39436188
    [Google Scholar]
39. Maiese K. Diabetes mellitus and glymphatic dysfunction: Roles for oxidative stress, mitochondria, circadian rhythm, artificial intelligence, and imaging. World J. Diabetes 2025 16 1 98948 10.4239/wjd.v16.i1.98948 39817214
    [Google Scholar]
40. Xie L. Cui S. Guo N. Li A. Zhang J. Research hotspots and frontiers of stem cells for Alzheimer’s disease. Chin. J. Tissue Eng. Res. 2025 29 7 1475 1485
    [Google Scholar]
41. Mosharaf M.P. Alam K. Gow J. Mahumud R.A. Mollah M.N.H. Common molecular and pathophysiological underpinnings of delirium and Alzheimer’s disease: Molecular signatures and therapeutic indications. BMC Geriatr. 2024 24 1 716 10.1186/s12877‑024‑05289‑3 39210294
    [Google Scholar]
42. Jellinger K.A. Cognitive impairment in multiple sclerosis: From phenomenology to neurobiological mechanisms. J. Neural Transm. 2024 131 8 871 899 10.1007/s00702‑024‑02786‑y 38761183
    [Google Scholar]
43. Shafiek M.S. Mekky R.Y. Nassar N.N. El-Yamany M.F. Rabie M.A. Vortioxetine ameliorates experimental autoimmune encephalomyelitis model of multiple sclerosis in mice via activation of PI3K/Akt/CREB/BDNF cascade and modulation of serotonergic pathway signaling. Eur. J. Pharmacol. 2024 982 176929 10.1016/j.ejphar.2024.176929 39181226
    [Google Scholar]
44. Maiese K. Clinical depression, the mechanistic target of rapamycin (mTOR), and forkhead transcription factors (FoxOs). Curr. Neurovasc. Res. 2023 20 4 429 433 10.2174/1567202620999230928124725 37767959
    [Google Scholar]
45. Aravapally P.S.N. Chandrasekar N. Verma A. Shah R.P. Strategic approaches to assess and quantify the oxidative stress biomarkers in complex biological systems. Bioanalysis 2025 17 8 561 574 10.1080/17576180.2025.2486929 40183176
    [Google Scholar]
46. Baser K.H.C. Haskologlu I.C. Erdag E. Molecular links between circadian rhythm disruption, melatonin, and neurodegenerative diseases: An updated review. Molecules 2025 30 9 1888 10.3390/molecules30091888 40363695
    [Google Scholar]
47. Khaitin A.M. Guzenko V.V. Bachurin S.S. Demyanenko S.V. c-Myc and FOXO3a—the everlasting decision between neural regeneration and degeneration. Int. J. Mol. Sci. 2024 25 23 12621 10.3390/ijms252312621 39684331
    [Google Scholar]
48. Maiese K. The mechanistic target of rapamycin (mTOR) and the silent mating-type information regulation 2 homolog 1 (SIRT1): Oversight for neurodegenerative disorders. Biochem. Soc. Trans. 2018 46 2 351 360 10.1042/BST20170121 29523769
    [Google Scholar]
49. Maiese K. The impact of aging and oxidative stress in metabolic and nervous system disorders: Programmed cell death and molecular signal transduction crosstalk. Front Immunol 2023 14 1273570 10.3389/fimmu.2023.1273570
    [Google Scholar]
50. Parab S. Parekh N. Apte K. Singh D. Kumawat V. Bagwe-Parab S. Unraveling the mechanisms of hydrophilic vitamins in Alzheimer’s and Parkinson’s: Preclinical and clinical evidence. Hydrophilic Vitamins in Health and Disease. Shah A.K. Tappia P.S. Dhalla N.S. Cham Advances in Biochemistry in Health and Disease Springer 2024 29 10.1007/978‑3‑031‑55474‑2_8
    [Google Scholar]
51. Shafie A. Ashour A.A. Anwar S. Anjum F. Hassan M.I. Exploring molecular mechanisms, therapeutic strategies, and clinical manifestations of Huntington’s disease. Arch. Pharm. Res. 2024 47 6 571 595 10.1007/s12272‑024‑01499‑w 38764004
    [Google Scholar]
52. Abdalla M.M.I. Insulin resistance as the molecular link between diabetes and Alzheimer’s disease. World J. Diabetes 2024 15 7 1430 1447 10.4239/wjd.v15.i7.1430 39099819
    [Google Scholar]
53. Kwok I. Lattie E.G. Yang D. Summers A. Cotten P. Leong C.A. Moskowitz J.T. Developing social enhancements for a web-based, positive emotion intervention for Alzheimer disease caregivers: Qualitative focus group and interview study. JMIR Form. Res. 2024 8 50234 10.2196/50234 38662432
    [Google Scholar]
54. Wertman E. Essential new complexity-based themes for patient-centered diagnosis and treatment of dementia and predementia in older people: Multimorbidity and multilevel phenomenology. J. Clin. Med. 2024 13 14 4202 10.3390/jcm13144202 39064242
    [Google Scholar]
55. Maiese K. Novel nervous and multi-system regenerative therapeutic strategies for diabetes mellitus with mTOR. Neural Regen. Res. 2016 11 3 372 385 10.4103/1673‑5374.179032 27127460
    [Google Scholar]
56. Maiese K. Impacting dementia and cognitive loss with innovative strategies: Mechanistic target of rapamycin, clock genes, circular non-coding ribonucleic acids, and Rho/Rock. Neural Regen. Res. 2019 14 5 773 774 10.4103/1673‑5374.249224 30688262
    [Google Scholar]
57. Maiese K. Cognitive impairment with diabetes mellitus and metabolic disease: Innovative insights with the mechanistic target of rapamycin and circadian clock gene pathways. Expert Rev. Clin. Pharmacol. 2020 13 1 23 34 10.1080/17512433.2020.1698288 31794280
    [Google Scholar]
58. Maiese K. Cornerstone cellular pathways for metabolic disorders and diabetes mellitus: Non-coding RNAs, wnt signaling, and AMPK. Cells 2023 12 22 2595 10.3390/cells12222595 37998330
    [Google Scholar]
59. Fessel J. Personalized, precision medicine to cure Alzheimer’s dementia: Approach #1. Int. J. Mol. Sci. 2024 25 7
    [Google Scholar]
60. Grimaldi L. Bovi E. Formisano R. Sancesario G. Apo E. ApoE: The non-protagonist actor in neurological diseases. Genes 2024 15 11 1397 10.3390/genes15111397 39596597
    [Google Scholar]
61. Ibrahim W.W. Sayed R.H. Abdelhameed M.F. Omara E.A. Nassar M.I. Abdelkader N.F. Farag M.A. Elshamy A.I. Afifi S.M. Neuroprotective potential of Erigeron bonariensis ethanolic extract against ovariectomized/D-galactose-induced memory impairments in female rats in relation to its metabolite fingerprint as revealed using UPLC/MS. Inflammopharmacology 2024 32 2 1091 1112 10.1007/s10787‑023‑01418‑3 38294617
    [Google Scholar]
62. Karati D. Meur S. Roy S. Mukherjee S. Debnath B. Jha S.K. Glycogen synthase kinase 3 (GSK3) inhibition: A potential therapeutic strategy for Alzheimer’s disease. Naunyn Schmiedebergs Arch. Pharmacol. 2024 39432068
    [Google Scholar]
63. Maiese K. Cognitive impairment and dementia: Gaining insight through circadian clock gene pathways. Biomolecules 2021 11 7 1002 10.3390/biom11071002 34356626
    [Google Scholar]
64. Maiese K. Cellular metabolism: A fundamental component of degeneration in the nervous system. Biomolecules 2023 13 5 816 10.3390/biom13050816 37238686
    [Google Scholar]
65. Nagarajan A. Laird J. Ugochukwu O. Reppe S. Gautvik K. Ross R.D. Bennett D.A. Rosen C. Kiel D.P. Higginbotham L.A. Seyfried N.T. Lary C.W. Network analysis of brain and bone tissue transcripts reveals shared molecular mechanisms underlying Alzheimer’s disease and related dementias and osteoporosis. J. Gerontol. A Biol. Sci. Med. Sci. 2024 79 11 glae211 10.1093/gerona/glae211 39194133
    [Google Scholar]
66. Tang H. Shaaban C.E. DeKosky S.T. Smith G.E. Hu X. Jaffee M. Salloum R.G. Bian J. Guo J. Association of education attainment, smoking status, and alcohol use disorder with dementia risk in older adults: A longitudinal observational study. Alzheimers Res. Ther. 2024 16 1 206 10.1186/s13195‑024‑01569‑7 39294787
    [Google Scholar]
67. Trujillo-Rangel W.Á. Acuña-Vaca S. Padilla-Ponce D.J. García-Mercado F.G. Torres-Mendoza B.M. Pacheco-Moises F.P. Escoto-Delgadillo M. García-Benavides L. Delgado-Lara D.L.C. Modulation of the circadian rhythm and oxidative stress as molecular targets to improve vascular dementia: A pharmacological perspective. Int. J. Mol. Sci. 2024 25 8 4401 10.3390/ijms25084401 38673986
    [Google Scholar]
68. Vargas K.G. Milic J. Zaciragic A. Wen K. Jaspers L. Nano J. Dhana K. Bramer W.M. Kraja B. van Beeck E. Ikram M.A. Muka T. Franco O.H. The functions of estrogen receptor beta in the female brain: A systematic review. Maturitas 2016 93 41 57 10.1016/j.maturitas.2016.05.014 27338976
    [Google Scholar]
69. Maiese K. Dysregulation of metabolic flexibility: The impact of mTOR on autophagy in neurodegenerative disease. Int. Rev. Neurobiol. 2020 155 1 35 10.1016/bs.irn.2020.01.009 32854851
    [Google Scholar]
70. Amidfar M. Garcez M.L. Kim Y.K. The shared molecular mechanisms underlying aging of the brain, major depressive disorder, and Alzheimer’s disease: The role of circadian rhythm disturbances. Prog. Neuropsychopharmacol. Biol. Psychiatry 2023 123 110721 10.1016/j.pnpbp.2023.110721 36702452
    [Google Scholar]
71. Maiese K. Moving to the rhythm with clock (circadian) genes, autophagy, mTOR, and SIRT1 in degenerative disease and cancer. Curr. Neurovasc. Res. 2017 14 3 299 304 28721811
    [Google Scholar]
72. Roccaro I. Smirni D. Fiat lux: The light became therapy. An overview on the bright light therapy in Alzheimer’s disease sleep disorders. J. Alzheimers Dis. 2020 77 1 113 125 10.3233/JAD‑200478 32804145
    [Google Scholar]
73. Liu B. Zhao G. Jin L. Shi J. Nicotinamide improves cognitive function in mice with chronic cerebral hypoperfusion. Front. Neurol. 2021 12 596641 10.3389/fneur.2021.596641 33569040
    [Google Scholar]
74. Na D. Lim D.H. Hong J.S. Lee H.M. Cho D. Yu M.S. Shaker B. Ren J. Lee B. Song J.G. Oh Y. Lee K. Oh K.S. Lee M.Y. Choi M.S. Choi H.S. Kim Y.H. Bui J.M. Lee K. Kim H.W. Lee Y.S. Gsponer J. A multi‐layered network model identifies Akt1 as a common modulator of neurodegeneration. Mol. Syst. Biol. 2023 19 12 11801 10.15252/msb.202311801 37984409
    [Google Scholar]
75. Maiese K. Targeting the core of neurodegeneration: FoxO, mTOR, and SIRT1. Neural Regen. Res. 2021 16 3 448 455 10.4103/1673‑5374.291382 32985464
    [Google Scholar]
76. Hadamitzky M. Herring A. Kirchhof J. Bendix I. Haight M.J. Keyvani K. Lückemann L. Unteroberdörster M. Schedlowski M. Repeated systemic treatment with rapamycin affects behavior and amygdala protein expression in rats. Int. J. Neuropsychopharmacol. 2018 21 6 592 602 10.1093/ijnp/pyy017 29462337
    [Google Scholar]
77. Colín-Martínez E. Espino-de-la-Fuente C. Arias C. Age- and sex-associated wnt signaling dysregulation is exacerbated from the early stages of neuropathology in an Alzheimer’s disease model. Neurochem. Res. 2024 49 11 3094 3104 10.1007/s11064‑024‑04224‑7 39167347
    [Google Scholar]
78. Maiese K. Microglia: Formidable players in Alzheimer’s disease and other neurodegenerative disorders. Curr. Neurovasc. Res. 2023 20 5 515 518 10.2174/1567202620999231027155308 37888824
    [Google Scholar]
79. Trisal A. Singh A.K. Clinical insights on caloric restriction mimetics for mitigating brain aging and related neurodegeneration. Cell. Mol. Neurobiol. 2024 44 1 67 10.1007/s10571‑024‑01493‑2 39412683
    [Google Scholar]
80. Ju D.T. Huang R.F.S. Tsai B.C.K. Su Y.C. Chiu P.L. Chang Y.M. Padma V.V. Ho T.J. Yao C.H. Kuo W.W. Huang C.Y. Folic acid and folinic acid protect hearts of aging triple-transgenic Alzheimer’s disease mice via IGF1R/PI3K/AKT and SIRT1/AMPK pathways. Neurotox. Res. 2023 41 6 648 659 10.1007/s12640‑023‑00666‑z 37707697
    [Google Scholar]
81. Maiese K. The metabolic basis for nervous system dysfunction in Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. Curr. Neurovasc. Res. 2023 20 3 314 333 10.2174/1567202620666230721122957 37488757
    [Google Scholar]
82. Zhang W. Huang Y. Guo X. Zhang M. Yuan X. Zu H. DHCR24 reverses Alzheimer’s disease-related pathology and cognitive impairment via increasing hippocampal cholesterol levels in 5xFAD mice. Acta Neuropathol. Commun. 2023 11 1 102 10.1186/s40478‑023‑01593‑y 37344916
    [Google Scholar]
83. Conze C. Trushina N.I. Monteiro-Abreu N. Singh L. Romero D.V. Wienbeuker E. Schwarze A.S. Holtmannspötter M. Bakota L. Brandt R. Redox signaling modulates axonal microtubule organization and induces a specific phosphorylation signature of microtubule-regulating proteins. Redox Biol. 2025 83 103626 10.1016/j.redox.2025.103626 40222271
    [Google Scholar]
84. Gupta S. Afzal M. Agrawal N. Almalki W.H. Rana M. Gangola S. Chinni S.V. Kumar K B. Ali H. Singh S.K. Jha S.K. Gupta G. Harnessing the FOXO-SIRT1 axis: Insights into cellular stress, metabolism, and aging. Biogerontology 2025 26 2 65 10.1007/s10522‑025‑10207‑0 40011269
    [Google Scholar]
85. Liu S. Liu T. Li J. Hong J. Moosavi-Movahedi A.A. Wei J. Type 2 diabetes mellitus exacerbates pathological processes of Parkinson’s disease: Insights from signaling pathways mediated by insulin receptors. Neurosci. Bull. 2025 41 4 676 690 10.1007/s12264‑024‑01342‑8 39754628
    [Google Scholar]
86. Maiese K. Nicotinamide as a foundation for treating neurodegenerative disease and metabolic disorders. Curr. Neurovasc. Res. 2021 18 1 134 149 10.2174/18755739MTEzaMDMw2 33397266
    [Google Scholar]
87. Maiese K. Fox O. FoxO transcription factors and regenerative pathways in diabetes mellitus. Curr. Neurovasc. Res. 2015 12 4 404 413 10.2174/1567202612666150807112524 26256004
    [Google Scholar]
88. Maiese K. Prospects and perspectives for WISP1 (CCN4) in diabetes mellitus. Curr. Neurovasc. Res. 2020 17 3 327 331 10.2174/1567202617666200327125257 32216738
    [Google Scholar]
89. Mohan M. Mannan A. Singh T.G. Unravelling the role of protein kinase R (PKR) in neurodegenerative disease: A review. Mol. Biol. Rep. 2025 52 1 377 10.1007/s11033‑025‑10484‑5 40205152
    [Google Scholar]
90. Pang J. Cen C. Tian Y. Cao X. Hao L. Tao X. Cao Z. Targeting Shp2 as a therapeutic strategy for neurodegenerative diseases. Transl. Psychiatry 2025 15 1 6 10.1038/s41398‑024‑03222‑1 39794316
    [Google Scholar]
91. Maiese K. Mitochondria, mitophagy, mitoptosis, and programmed cell death: Implications from aging to cancer. Curr. Neurovasc. Res. 2024 21 1 1 5 10.2174/1567202621999240118155618 38251666
    [Google Scholar]
92. Shen Y. Chen Q.C. Li C.Y. Han F.J. Independent organelle and organelle—organelle interactions: Essential mechanisms for malignant gynecological cancer cell survival. Front. Immunol. 2024 15 1393852 10.3389/fimmu.2024.1393852 38711526
    [Google Scholar]
93. Zhou R. Barnes K. Gibson S. Fillmore N. Dual-edged role of SIRT1 in energy metabolism and cardiovascular disease. Am. J. Physiol. Heart Circ. Physiol. 2024 327 5 H1162 H1173 10.1152/ajpheart.00001.2024 39269450
    [Google Scholar]
94. Zhu G. Zuo Q. Liu S. Zheng P. Zhang Y. Zhang X. Rollins J.A. Liu J. Pan H. A FOX transcription factor phosphorylated for regulation of autophagy facilitates fruiting body development in Sclerotinia sclerotiorum. New Phytol. 2025 246 6 2683 2701 10.1111/nph.70151 40248859
    [Google Scholar]
95. Gao F. Yang Z. Li J. The miR-34a-5p promotes hippocampal neuronal ferroptosis in epilepsy by regulating SIRT1. Neurochem. Res. 2025 50 2 124 10.1007/s11064‑025‑04378‑y 40126751
    [Google Scholar]
96. Han G. Hu K. Luo T. Wang W. Zhang D. Ouyang L. Liu X. Liu J. Wu Y. Liang J. Ling J. Chen Y. Xuan R. Zhang J. Yu P. Research progress of non-coding RNA regulating the role of PANoptosis in diabetes mellitus and its complications. Apoptosis 2025 30 3-4 516 536 10.1007/s10495‑024‑02066‑w 39755822
    [Google Scholar]
97. Dzik K.P. Flis D.J. Kaczor-Keller K.B. Bytowska Z.K. Karnia M.J. Ziółkowski W. Kaczor J.J. Spinal cord abnormal autophagy and mitochondria energy metabolism are modified by swim training in SOD1-G93A mice. J. Mol. Med. 2024 102 3 379 390 10.1007/s00109‑023‑02410‑8 38197966
    [Google Scholar]
98. Maiese K. New insights for nicotinamide Metabolic disease autophagy and mTOR. Front. Biosci. 2020 25 11 1925 1973 10.2741/4886 32472766
    [Google Scholar]
99. Maiese K. Innovative therapeutic strategies for cardiovascular disease. EXCLI J. 2023 22 690 715 37593239
    [Google Scholar]
100. Foser S. Maiese K. Digumarthy S.R. Puig-Butille J.A. Rebhan C. Looking to the future of early detection in cancer: Liquid biopsies, imaging, and artificial intelligence. Clin. Chem. 2024 70 1 27 32 10.1093/clinchem/hvad196 38175601
     [Google Scholar]
101. Maiese K. Cardiovascular and nonalcoholic fatty liver disease: Sharing common ground through SIRT1 pathways. World J. Cardiol. 2024 16 11 632 643 10.4330/wjc.v16.i11.632 39600987
     [Google Scholar]
102. Klionsky D.J. Abdel-Aziz A.K. Abdelfatah S. Abdellatif M. Abdoli A. Abel S. Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy 2021 17 1 1 382
     [Google Scholar]
103. Maiese K. Chong Z.Z. Shang Y.C. Wang S. mTOR: On target for novel therapeutic strategies in the nervous system. Trends Mol. Med. 2013 19 1 51 60 10.1016/j.molmed.2012.11.001 23265840
     [Google Scholar]
104. Fu J. Du M. Wu B. Wu C. Li X. Tan W. Huang X. Zhu Z. Zhang J. Liao Z.B. CircRNA Itm2b induces oxidative stress via the interaction with Sirt1-Nox4 to aggravate sleep disturbances after traumatic brain injury. Cell Biosci. 2025 15 1 21 10.1186/s13578‑025‑01353‑6 39962534
     [Google Scholar]
105. Chen Y.C. Wang W.S. Lewis S.J.G. Wu S.L. Fighting against the clock: Circadian disruption and Parkinson’s disease. J. Mov. Disord. 2024 17 1 1 14 10.14802/jmd.23216 37989149
     [Google Scholar]
106. Di T. Guo M. Xu J. Feng C. Du Y. Wang L. Chen Y. Circadian clock genes REV-ERBα regulates the secretion of IL-1β in deciduous tooth pulp stem cells by regulating autophagy in the process of physiological root resorption of deciduous teeth. Dev. Biol. 2024 510 8 16 10.1016/j.ydbio.2024.02.008 38403101
     [Google Scholar]
107. Di T. Zhou Z. Liu F. Chen Y. Wang L. Autophagy and circadian rhythms: Interactions and clinical implications. Biocell 2024 48 1 33 45 10.32604/biocell.2023.031638
     [Google Scholar]
108. Maiese K. Neurodegeneration, memory loss, and dementia: The impact of biological clocks and circadian rhythm. Front. Biosci. 2021 26 9 614 627 10.52586/4971 34590471
     [Google Scholar]
109. Mielecki D. Bratek-Gerej E. Salińska E. Metabotropic glutamate receptors—guardians and gatekeepers in neonatal hypoxic-ischemic brain injury. Pharmacol. Rep. 2024 76 6 1272 1285 10.1007/s43440‑024‑00653‑x 39289333
     [Google Scholar]
110. Eyob W. George A.K. Homme R.P. Stanisic D. Sandhu H. Tyagi S.C. Singh M. Regulation of the parental gene GRM4 by circGrm4 RNA transcript and glutamate-mediated neurovascular toxicity in eyes. Mol. Cell. Biochem. 2021 476 2 663 673 10.1007/s11010‑020‑03934‑0 33074445
     [Google Scholar]
111. Zhang Z. Zheng X. Liu Y. Luan Y. Wang L. Zhao L. Zhang J. Tian Y. Lu H. Chen X. Liu Y. Activation of metabotropic glutamate receptor 4 regulates proliferation and neural differentiation in neural stem/progenitor cells of the rat subventricular zone and increases phosphatase and tensin homolog protein expression. J. Neurochem. 2021 156 4 465 480 10.1111/jnc.14984 32052426
     [Google Scholar]
112. Chong Z.Z. Li F. Maiese K. Oxidative stress in the brain: Novel cellular targets that govern survival during neurodegenerative disease. Prog. Neurobiol. 2005 75 3 207 246 10.1016/j.pneurobio.2005.02.004 15882775
     [Google Scholar]
113. Maiese K. Chong Z. Li F. Driving cellular plasticity and survival through the signal transduction pathways of metabotropic glutamate receptors. Curr. Neurovasc. Res. 2005 2 5 425 446 10.2174/156720205774962692 16375723
     [Google Scholar]
114. Maiese K. Chong Z.Z. Shang Y.C. Hou J. Therapeutic promise and principles: Metabotropic glutamate receptors. Oxid. Med. Cell. Longev. 2008 1 1 1 14 10.4161/oxim.1.1.6842 19750024
     [Google Scholar]
115. Ali T. Rahman S.U. Hao Q. Li W. Liu Z. Ali Shah F. Murtaza I. Zhang Z. Yang X. Liu G. Li S. Melatonin prevents neuroinflammation and relieves depression by attenuating autophagy impairment through FOXO3a regulation. J. Pineal Res. 2020 69 2 12667 10.1111/jpi.12667 32375205
     [Google Scholar]
116. Gu S. Li Y. Jiang Y. Huang J.H. Wang F. Glymphatic dysfunction induced oxidative stress and neuro-inflammation in major depression disorders. Antioxidants 2022 11 11 22 96 10.3390/antiox11112296
     [Google Scholar]
117. Sakai M. Yu Z. Hirayama R. Nakasato M. Kikuchi Y. Ono C. Komatsu H. Nakanishi M. Yoshii H. Stellwagen D. Furuyashiki T. Komatsu M. Tomita H. Deficient autophagy in microglia aggravates repeated social defeat stress-induced social avoidance. Neural Plast. 2022 2022 1 13 10.1155/2022/7503553 35222638
     [Google Scholar]
118. Tai S.H. Chao L.C. Huang S.Y. Lin H.W. Lee A.H. Chen Y.Y. Lee E.J. Nicotinamide deteriorates post-stroke immunodepression following cerebral ischemia–reperfusion injury in mice. Biomedicines 2023 11 8 2145 10.3390/biomedicines11082145 37626642
     [Google Scholar]
119. Adhikari U.K. Khan R. Mikhael M. Balez R. David M.A. Mahns D. Hardy J. Tayebi M. Therapeutic anti‐amyloid β antibodies cause neuronal disturbances. Alzheimers Dement. 2023 19 6 2479 2496 10.1002/alz.12833 36515320
     [Google Scholar]
120. Fangma Y. Wan H. Shao C. Jin L. He Y. Research progress on the role of sirtuin 1 in cerebral ischemia. Cell. Mol. Neurobiol. 2023 43 5 1769 1783 10.1007/s10571‑022‑01288‑3 36153473
     [Google Scholar]
121. Inoue M. Tanida T. Kondo T. Takenaka S. Nakajima T. Oxygen-glucose deprivation-induced glial cell reactivity in the rat primary neuron-glia co-culture. J. Vet. Med. Sci. 2023 85 8 799 808 10.1292/jvms.23‑0175 37407448
     [Google Scholar]
122. Maiese K. Targeting molecules to medicine with mTOR, autophagy and neurodegenerative disorders. Br. J. Clin. Pharmacol. 2016 82 5 1245 1266 10.1111/bcp.12804 26469771
     [Google Scholar]
123. Gao J. Xu H. Rong Z. Chen L. Wnt family member 1 (Wnt1) overexpression-induced M2 polarization of microglia alleviates inflammation-sensitized neonatal brain injuries. Bioengineered 2022 13 5 12409 12420 10.1080/21655979.2022.2074767 35603707
     [Google Scholar]
124. González-Fernández C. González P. González-Pérez F. Rodríguez F.J. Characterization of ex vivo and in vitro wnt transcriptome induced by spinal cord injury in rat microglial cells. Brain Sci. 2022 12 6 708 10.3390/brainsci12060708 35741593
     [Google Scholar]
125. Shang Y.C. Chong Z.Z. Hou J. Maiese K. Wnt1, FoxO3a, and NF-κB oversee microglial integrity and activation during oxidant stress. Cell. Signal. 2010 22 9 1317 1329 10.1016/j.cellsig.2010.04.009 20462515
     [Google Scholar]
126. Shang Y.C. Chong Z.Z. Wang S. Maiese K. Prevention of β-amyloid degeneration of microglia by erythropoietin depends on Wnt1, the PI 3-K/mTOR pathway, Bad, and Bcl-xL. Aging 2012 4 3 187 201 10.18632/aging.100440 22388478
     [Google Scholar]
127. Rangarajan P. Karthikeyan A. Lu J. Ling E.A. Dheen S.T. Sirtuin 3 regulates Foxo3a-mediated antioxidant pathway in microglia. Neuroscience 2015 311 398 414 10.1016/j.neuroscience.2015.10.048 26523980
     [Google Scholar]
128. Wang Y. Lin Y. Wang L. Zhan H. Luo X. Zeng Y. Wu W. Zhang X. Wang F. TREM2 ameliorates neuroinflammatory response and cognitive impairment via PI3K/AKT/FoxO3a signaling pathway in Alzheimer’s disease mice. Aging 2020 12 20 20862 20879 10.18632/aging.104104 33065553
     [Google Scholar]
129. Maiese K. Chong Z.Z. Hou J. Shang Y.C. Oxidative stress: Biomarkers and novel therapeutic pathways. Exp. Gerontol. 2010 45 3 217 234 10.1016/j.exger.2010.01.004 20064603
     [Google Scholar]
130. Maiese K. Chong Z.Z. Shang Y.C. OutFOXOing disease and disability: The therapeutic potential of targeting FoxO proteins. Trends Mol. Med. 2008 14 5 219 227 10.1016/j.molmed.2008.03.002 18403263
     [Google Scholar]
131. Loane D.J. Stoica B.A. Byrnes K.R. Jeong W. Faden A.I. Activation of mGluR5 and inhibition of NADPH oxidase improves functional recovery after traumatic brain injury. J. Neurotrauma 2013 30 5 403 412 10.1089/neu.2012.2589 23199080
     [Google Scholar]
132. Williams C.J. Dexter D.T. Neuroprotective and symptomatic effects of targeting group III mG lu receptors in neurodegenerative disease. J. Neurochem. 2014 129 1 4 20 10.1111/jnc.12608 24224472
     [Google Scholar]
133. Lin S.H. Maiese K. The metabotropic glutamate receptor system protects against ischemic free radical programmed cell death in rat brain endothelial cells. J. Cereb. Blood Flow Metab. 2001 21 3 262 275 10.1097/00004647‑200103000‑00010 11295881
     [Google Scholar]
134. Maiese K. Cellular mechanisms of neuronal protection by metabotropic glutamate receptors. Frontiers in Cerebrovascular Disease: Mechanisms, Diagnosis, and Treatment Robertson JT. Nowak T.S. Armonk, NY Futura Publishing Company, Inc. 1998 281 297
     [Google Scholar]
135. Sun N. Victor M.B. Park Y.P. Xiong X. Scannail A.N. Leary N. Prosper S. Viswanathan S. Luna X. Boix C.A. James B.T. Tanigawa Y. Galani K. Mathys H. Jiang X. Ng A.P. Bennett D.A. Tsai L.H. Kellis M. Human microglial state dynamics in Alzheimer’s disease progression. Cell 2023 186 20 4386 4403.e29 10.1016/j.cell.2023.08.037 37774678
     [Google Scholar]
136. Haratizadeh S. Nemati M. Basiri M. Nozari M. Erythropoietin and glial cells in central and peripheral nervous systems. Mol. Biol. Rep. 2024 51 1 1065 10.1007/s11033‑024‑09997‑2 39422776
     [Google Scholar]
137. Samuels J.D. Lukens J.R. Price R.J. Emerging roles for ITAM and ITIM receptor signaling in microglial biology and Alzheimer’s disease-related amyloidosis. J. Neurochem. 2024 168 10 3558 3573 37822118
     [Google Scholar]
138. Fessel J. Cure of Alzheimer’s dementia requires addressing all of the affected brain cell types. J. Clin. Med. 2023 12 5 2049 10.3390/jcm12052049 36902833
     [Google Scholar]
139. Wang M. Zhang S. Liu X. Wang P. Zhu Y. Zhu J. Lv C. Li S. Liu S. Wen L. Salvianolic acid B ameliorates retinal deficits in an early-stage Alzheimer’s disease mouse model through downregulating BACE1 and Aβ generation. Acta Pharmacol. Sin. 2023 44 11 2151 2168 10.1038/s41401‑023‑01125‑3 37420104
     [Google Scholar]
140. Wang R. Zhu Y. Qin L.F. Xu Z.G. Gao X.R. Liu C.B. Xu G.T. Chen Y.Z. Comprehensive bibliometric analysis of stem cell research in Alzheimer’s disease from 2004 to 2022. Dement. Geriatr. Cogn. Disord. 2023 52 2 47 73 10.1159/000528886 37068473
     [Google Scholar]
141. Morris G. Berk M. Maes M. Puri B.K. Could Alzheimer’s disease originate in the periphery and if so how so? Mol. Neurobiol. 2019 56 1 406 434 10.1007/s12035‑018‑1092‑y 29705945
     [Google Scholar]
142. Carobene A. Maiese K. Abou-Diwan C. Locatelli M. Serteser M. Coskun A. Unsal I. Biological variation estimates for serum neurofilament light chain in healthy subjects. Clin. Chim. Acta 2023 551 117608 10.1016/j.cca.2023.117608 37844678
     [Google Scholar]
143. Li X. Li K. Chu F. Huang J. Yang Z. Graphene oxide enhances β-amyloid clearance by inducing autophagy of microglia and neurons. Chem. Biol. Interact. 2020 325 109126 10.1016/j.cbi.2020.109126 32430275
     [Google Scholar]