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Abstract

Neurological disorders are brain conditions characterized by the loss of nerve cells, leading to a decline in function. Standard examples include dementia, tremors, involuntary movements, muscle weakness, and autoimmune attacks. The most common form of dementia is Alzheimer's, affecting over 5 million elderly individuals, while tremors, stiffness, and slow movement are caused by Parkinson's. Involuntary movements and emotional problems are caused by Huntington's, while muscle weakness and eventual demise are caused by Amyotrophic lateral sclerosis. Vision problems, fatigue, and difficulty walking are caused by Multiple sclerosis (MS), an autoimmune disease that attacks the myelin sheath. models provide cost and complexity reduction, environmental control, and high-throughput. Researchers employ both cell-based () and animal-based () models to investigate neurodegenerative illnesses and endeavor to formulate novel treatments for diverse conditions. models provide cost and complexity reduction, environment control, and high-throughput screening of potential therapeutic agents compared to models. Nevertheless, they possess constraints, including the absence of intricate interactions that transpire in the entire organism and the inability to reproduce the disease progression completely.

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2025-06-24
2025-10-19

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References

  1. Abdeltawab M.S.A. Abdel-Shafi I.R. Aboulhoda B.E. Mahfoz A.M. Hamed A.M.R. The neuroprotective potential of curcumin on T. Spiralis infected mice. BMC Complementary Med Ther 2024 24 1 99 10.1186/s12906‑024‑04399‑0 38388410
    [Google Scholar]
  2. Tanaka M. Toldi J. Vécsei L. Exploring the etiological links behind neurodegenerative diseases: Inflammatory cytokines and bioactive kynurenines. Int. J. Mol. Sci. 2020 21 7 2431 10.3390/ijms21072431 32244523
    [Google Scholar]
  3. Hansson O. Biomarkers for neurodegenerative diseases. Nat. Med. 2021 27 6 954 963 10.1038/s41591‑021‑01382‑x 34083813
    [Google Scholar]
  4. Alzheimer's 2018 Alzheimer’s disease facts and figures. Alzheimers Dement. 2018 14 3 367 429 10.1016/j.jalz.2018.02.001
    [Google Scholar]
  5. Itoh Y. Voskuhl R.R. Cell specificity dictates similarities in gene expression in multiple sclerosis, Parkinson’s disease, and Alzheimer’s disease. PLoS One 2017 12 7 e0181349 10.1371/journal.pone.0181349 28715462
    [Google Scholar]
  6. Bashir H. Emerging therapies in Huntington’s disease. Expert Rev. Neurother. 2019 19 10 983 995 10.1080/14737175.2019.1631161 31181964
    [Google Scholar]
  7. Achenbach J. Thiels C. Lücke T. Saft C. Clinical manifestation of juvenile and pediatric HD patients: A retrospective case series. Brain Sci. 2020 10 6 340 10.3390/brainsci10060340 32503138
    [Google Scholar]
  8. Bakels H.S. Roos R.A.C. van Roon-Mom W.M.C. de Bot S.T. Juvenile-onset Huntington disease pathophysiology and neurodevelopment: A review. Mov. Disord. 2022 37 1 16 24 10.1002/mds.28823 34636452
    [Google Scholar]
  9. Tsvetkova D. Ivanova S. Obreshkova D. Neurodegenerative multioethiology Lou Gehrig’s disease–genetic mutations, pharmacological mechanisms and applications of rilusole. Int. J. Pharm. Res. Allied Sci. 2023 12 3 61 70 10.51847/w9fRJSNXjp
    [Google Scholar]
  10. Veronese S. Gallo G. Valle A. Cugno C. Chiò A. Calvo A. Cavalla P. Zibetti M. Rivoiro C. Oliver D.J. Specialist palliative care improves the quality of life in advanced neurodegenerative disorders: NE-PAL, a pilot randomised controlled study. BMJ Support. Palliat. Care 2017 7 2 164 172 10.1136/bmjspcare‑2014‑000788 26182947
    [Google Scholar]
  11. Colle D. Farina M. Ceccatelli S. Raciti M. Paraquat and maneb exposure alters rat neural stem cell proliferation by inducing oxidative stress: New insights on pesticide-induced neurodevelopmental toxicity. Neurotox. Res. 2018 34 4 820 833 10.1007/s12640‑018‑9916‑0 29859004
    [Google Scholar]
  12. Domenighetti C. Sugier P.E. Sreelatha A.A.K. Schulte C. Grover S. Mohamed O. Portugal B. May P. Bobbili D.R. Radivojkov-Blagojevic M. Lichtner P. Singleton A.B. Hernandez D.G. Edsall C. Mellick G.D. Zimprich A. Pirker W. Rogaeva E. Lang A.E. Koks S. Taba P. Lesage S. Brice A. Corvol J.C. Chartier-Harlin M.C. Mutez E. Brockmann K. Deutschländer A.B. Hadjigeorgiou G.M. Dardiotis E. Stefanis L. Simitsi A.M. Valente E.M. Petrucci S. Duga S. Straniero L. Zecchinelli A. Pezzoli G. Brighina L. Ferrarese C. Annesi G. Quattrone A. Gagliardi M. Matsuo H. Kawamura Y. Hattori N. Nishioka K. Chung S.J. Kim Y.J. Kolber P. van de Warrenburg B.P.C. Bloem B.R. Aasly J. Toft M. Pihlstrøm L. Guedes L.C. Ferreira J.J. Bardien S. Carr J. Tolosa E. Ezquerra M. Pastor P. Diez-Fairen M. Wirdefeldt K. Pedersen N.L. Ran C. Belin A.C. Puschmann A. Hellberg C. Clarke C.E. Morrison K.E. Tan M. Krainc D. Burbulla L.F. Farrer M.J. Krüger R. Gasser T. Sharma M. Elbaz A. Comprehensive Unbiaised Risk Factor Assessment for Genetics and Environment in Parkinson’s Disease (Courage-PD) consortium Mendelian randomisation study of smoking, alcohol, and coffee drinking in relation to Parkinson’s disease. J. Parkinsons Dis. 2022 12 1 267 282 10.3233/JPD‑212851 34633332
    [Google Scholar]
  13. Ball N. Teo W.P. Chandra S. Chapman J. Parkinson’s disease and the environment. Front. Neurol. 2019 10 218 10.3389/fneur.2019.00218 30941085
    [Google Scholar]
  14. Tarnacka B. Jopowicz A. Maślińska M. Copper, iron, and manganese toxicity in neuropsychiatric conditions. Int. J. Mol. Sci. 2021 22 15 7820 10.3390/ijms22157820 34360586
    [Google Scholar]
  15. Spencer P.S. Berntsson S.G. Buguet A. Butterfield P. Calne D.B. Calne S.M. Giménez-Roldán S. Hugon J. Kahlon S. Kisby G.E. Lagrange E. Landtblom A.M.E. Ludolph A.C. Nunn P.B. Palmer V.S. Reis J. Román G.C. Sipilä J.O.T. Spencer S.S. Angues R.V. Vernoux J.P. Yabushita M. Brain health: Pathway to primary prevention of neurodegenerative disorders of environmental origin. J. Neurol. Sci. 2025 468 123340 10.1016/j.jns.2024.123340 39667295
    [Google Scholar]
  16. Feigin V.L. Vos T. Nichols E. Owolabi M.O. Carroll W.M. Dichgans M. Deuschl G. Parmar P. Brainin M. Murray C. The global burden of neurological disorders: Translating evidence into policy. Lancet Neurol. 2020 19 3 255 265 10.1016/S1474‑4422(19)30411‑9 31813850
    [Google Scholar]
  17. Logroscino G. Urso D. Savica R. Descriptive epidemiology of neurodegenerative diseases: What are the critical questions? Neuroepidemiology 2022 56 5 309 318 10.1159/000525639 35728570
    [Google Scholar]
  18. Pohl F. Lin PKT The potential use of plant natural products and plant extracts with antioxidant properties for the prevention/treatment of neurodegenerative diseases: In vitro, in vivo and clinical trials. Molecules 2018 23 12 3283 10.3390/molecules23123283 30544977
    [Google Scholar]
  19. D’Antoni C. Mautone L. Sanchini C. Tondo L. Grassmann G. Cidonio G. Bezzi P. Cordella F. Di Angelantonio S. Unlocking neural function with 3D in vitro models: A technical review of self-assembled, guided, and bioprinted brain organoids and their applications in the study of neurodevelopmental and neurodegenerative disorders. Int. J. Mol. Sci. 2023 24 13 10762 10.3390/ijms241310762 37445940
    [Google Scholar]
  20. Segeritz C-P. Vallier L. Cell culture: Growing cells as model systems in vitro. Basic science methods for clinical researchers. Elsevier 2017 151 172 10.1016/B978‑0‑12‑803077‑6.00009‑6
    [Google Scholar]
  21. Li A. Pereira C. Hill E.E. Vukcevich O. Wang A. In vitro, in vivo and ex vivo models for peripheral nerve injury and regeneration. Curr. Neuropharmacol. 2022 20 2 344 361 10.2174/1570159X19666210407155543 33827409
    [Google Scholar]
  22. Marvian A.T. Koss D.J. Aliakbari F. Morshedi D. Outeiro T.F. In vitro models of synucleinopathies: Informing on molecular mechanisms and protective strategies. J. Neurochem. 2019 150 5 535 565 10.1111/jnc.14707 31004503
    [Google Scholar]
  23. Dunkel P. Chai C.L.L. Sperlágh B. Huleatt P.B. Mátyus P. Clinical utility of neuroprotective agents in neurodegenerative diseases: Current status of drug development for Alzheimer’s, Parkinson’s and Huntington’s diseases, and amyotrophic lateral sclerosis. Expert Opin. Investig. Drugs 2012 21 9 1267 1308 10.1517/13543784.2012.703178 22741814
    [Google Scholar]
  24. Slanzi A. Iannoto G. Rossi B. Zenaro E. Constantin G. In vitro models of neurodegenerative diseases. Front. Cell Dev. Biol. 2020 8 328 10.3389/fcell.2020.00328 32528949
    [Google Scholar]
  25. Louit A. Galbraith T. Berthod F. In vitro 3D modeling of neurodegenerative diseases. Bioengineering 2023 10 1 93 10.3390/bioengineering10010093 36671665
    [Google Scholar]
  26. Miny L. Maisonneuve B.G.C. Quadrio I. Honegger T. Modeling neurodegenerative diseases using in vitro compartmentalized microfluidic devices. Front. Bioeng. Biotechnol. 2022 10 919646 10.3389/fbioe.2022.919646 35813998
    [Google Scholar]
  27. Osaki T. Shin Y. Sivathanu V. Campisi M. Kamm R.D. In vitro microfluidic models for neurodegenerative disorders. Adv. Healthc. Mater. 2018 7 2 1700489 10.1002/adhm.201700489 28881425
    [Google Scholar]
  28. Haenseler W. Rajendran L. Concise review: Modeling neurodegenerative diseases with human pluripotent stem cell-derived microglia. Stem Cells 2019 37 6 724 730 10.1002/stem.2995 30801863
    [Google Scholar]
  29. Holloway P.M. Willaime-Morawek S. Siow R. Barber M. Owens R.M. Sharma A.D. Rowan W. Hill E. Zagnoni M. Advances in microfluidic in vitro systems for neurological disease modeling. J. Neurosci. Res. 2021 99 5 1276 1307 10.1002/jnr.24794 33583054
    [Google Scholar]
  30. Fanizza F. Campanile M. Forloni G. Giordano C. Albani D. Induced pluripotent stem cell-based organ-on-a-chip as personalized drug screening tools: A focus on neurodegenerative disorders. J. Tissue Eng. 2022 13 20417314221095339 10.1177/20417314221095339 35570845
    [Google Scholar]
  31. Cummings J. Montes A. Kamboj S. Cacho J.F. The role of basket trials in drug development for neurodegenerative disorders. Alzheimers Res. Ther. 2022 14 1 73 10.1186/s13195‑022‑01015‑6 35614479
    [Google Scholar]
  32. Matthews D.C. Mao X. Dowd K. Tsakanikas D. Jiang C.S. Meuser C. Andrews R.D. Lukic A.S. Lee J. Hampilos N. Shafiian N. Sano M. David Mozley P. Fillit H. McEwen B.S. Shungu D.C. Pereira A.C. Riluzole, a glutamate modulator, slows cerebral glucose metabolism decline in patients with Alzheimer’s disease. Brain 2021 144 12 3742 3755 10.1093/brain/awab222 34145880
    [Google Scholar]
  33. Shin C.Y. Kim H.S. Cha K.H. Won D.H. Lee J.Y. Jang S.W. Sohn U.D. The effects of donepezil, an acetylcholinesterase inhibitor, on impaired learning and memory in rodents. Biomol. Ther. 2018 26 3 274 281 10.4062/biomolther.2017.189 29463072
    [Google Scholar]
  34. Calabresi P. Ghiglieri V. Mazzocchetti P. Corbelli I. Picconi B. Levodopa-induced plasticity: A double-edged sword in Parkinson’s disease? Philos. Trans. R. Soc. Lond. B Biol. Sci. 2015 370 1672 20140184 10.1098/rstb.2014.0184 26009763
    [Google Scholar]
  35. Bhalerao A. Sivandzade F. Archie S.R. Chowdhury E.A. Noorani B. Cucullo L. In vitro modeling of the neurovascular unit: Advances in the field. Fluids Barriers CNS 2020 17 1 22 10.1186/s12987‑020‑00183‑7 32178700
    [Google Scholar]
  36. Perretta G. Non-human primate models in neuroscience research. Scand. J. Lab. Anim. Sci. 2009 36 1 77 85
    [Google Scholar]
  37. Tello J.A. Williams H.E. Eppler R.M. Steinhilb M.L. Khanna M. Animal models of neurodegenerative disease: Recent advances in fly highlight innovative approaches to drug discovery. Front. Mol. Neurosci. 2022 15 883358 10.3389/fnmol.2022.883358 35514431
    [Google Scholar]
  38. Vissers M.F.J.M. Heuberger J.A.A.C. Groeneveld G.J. Targeting for success: Demonstrating proof-of-concept with mechanistic early phase clinical pharmacology studies for disease-modification in neurodegenerative disorders. Int. J. Mol. Sci. 2021 22 4 1615 10.3390/ijms22041615 33562713
    [Google Scholar]
  39. Rizzo SJS Crawley J.N. Behavioral phenotyping assays for genetic mouse models of neurodevelopmental, neurodegenerative, and psychiatric disorders. Annu. Rev. Anim. Biosci. 2017 5 1 371 389 10.1146/annurev‑animal‑022516‑022754 28199172
    [Google Scholar]
  40. Ruan J. Yao Y. Behavioral tests in rodent models of stroke. Brain Hemorrhages 2020 1 4 171 184 10.1016/j.hest.2020.09.001 34322665
    [Google Scholar]
  41. Korte SM De Boer S.F. A robust animal model of state anxiety: Fear-potentiated behaviour in the elevated plus-maze. Eur. J. Pharmacol. 2003 463 1-3 163 175 10.1016/S0014‑2999(03)01279‑2 12600708
    [Google Scholar]
  42. Huang P. Zhang M. Magnetic resonance imaging studies of neurodegenerative disease: From methods to translational research. Neurosci. Bull. 2023 39 1 99 112 10.1007/s12264‑022‑00905‑x 35771383
    [Google Scholar]
  43. Chen J.J. Functional MRI of brain physiology in aging and neurodegenerative diseases. Neuroimage 2019 187 209 225 10.1016/j.neuroimage.2018.05.050 29793062
    [Google Scholar]
  44. Leuzy A. Chiotis K. Lemoine L. Gillberg P.G. Almkvist O. Rodriguez-Vieitez E. Nordberg A. Tau PET imaging in neurodegenerative tauopathies—still a challenge. Mol. Psychiatry 2019 24 8 1112 1134 10.1038/s41380‑018‑0342‑8 30635637
    [Google Scholar]
  45. Ehrenberg A.J. Relevance of biomarkers across different neurodegenerative diseases. Alzheimers Res. Ther. 2020 12 1 11
    [Google Scholar]
  46. Amartumur S. Nguyen H. Huynh T. Kim T.S. Woo R.S. Oh E. Kim K.K. Lee L.P. Heo C. Neuropathogenesis-on-chips for neurodegenerative diseases. Nat. Commun. 2024 15 1 2219 10.1038/s41467‑024‑46554‑8 38472255
    [Google Scholar]
  47. Rey F. Barzaghini B. Nardini A. Bordoni M. Zuccotti G.V. Cereda C. Raimondi M.T. Carelli S. Advances in tissue engineering and innovative fabrication techniques for 3-D-structures: Translational applications in neurodegenerative diseases. Cells 2020 9 7 1636 10.3390/cells9071636 32646008
    [Google Scholar]
  48. Pandey S. Jirásko M. Lochman J. Chvátal A. Dvorakova MC Kučera R. iPSCs in neurodegenerative disorders: A unique platform for clinical research and personalized medicine. J. Pers. Med. 2022 12 9 1485 10.3390/jpm12091485 36143270
    [Google Scholar]
  49. Nwabufo C.K. Aigbogun O.P. Diagnostic and therapeutic agents that target alpha-synuclein in Parkinson’s disease. J. Neurol. 2022 269 11 5762 5786 10.1007/s00415‑022‑11267‑9 35831620
    [Google Scholar]
  50. Obrador E. Salvador-Palmer R. López-Blanch R. Dellinger R.W. Estrela J.M. NAD+ precursors and antioxidants for the treatment of amyotrophic lateral sclerosis. Biomedicines 2021 9 8 1000 10.3390/biomedicines9081000 34440204
    [Google Scholar]
  51. Hubrecht R.C. Carter E. The 3Rs and humane experimental technique: Implementing change. Animals 2019 9 10 754 10.3390/ani9100754 31575048
    [Google Scholar]
  52. Domínguez-Oliva A. Hernández-Ávalos I. Martínez-Burnes J. Olmos-Hernández A. Verduzco-Mendoza A. Mota-Rojas D. The importance of animal models in biomedical research: Current insights and applications. Animals 2023 13 7 1223 10.3390/ani13071223 37048478
    [Google Scholar]
  53. Holm A. Hansen S.N. Klitgaard H. Kauppinen S. Clinical advances of RNA therapeutics for treatment of neurological and neuromuscular diseases. RNA Biol. 2022 19 1 594 608 10.1080/15476286.2022.2066334 35482908
    [Google Scholar]
  54. Singh A. Kukreti R. Saso L. Kukreti S. Oxidative stress: A key modulator in neurodegenerative diseases. Molecules 2019 24 8 1583 10.3390/molecules24081583 31013638
    [Google Scholar]
  55. Solana-Manrique C. Sánchez-Pérez A.M. Paricio N. Muñoz-Descalzo S. Two- and three-dimensional in vitro models of Parkinson’s and Alzheimer’s diseases: State-of-the-art and applications. Int. J. Mol. Sci. 2025 26 2 620 10.3390/ijms26020620 39859333
    [Google Scholar]
  56. Masserdotti G. Late onset Alzheimer’s disease: Modeling disease hallmarks via in vitro 3D iNeuron cultures. Signal Transduct. Target. Ther. 2024 9 1 284 10.1038/s41392‑024‑01999‑7 39389939
    [Google Scholar]
  57. Balestri W. Sharma R. da Silva V.A. Bobotis B.C. Curle A.J. Kothakota V. Kalantarnia F. Hangad M.V. Hoorfar M. Jones J.L. Tremblay M.È. El-Jawhari J.J. Willerth S.M. Reinwald Y. Modeling the neuroimmune system in Alzheimer’s and Parkinson’s diseases. J. Neuroinflammation 2024 21 1 32 10.1186/s12974‑024‑03024‑8 38263227
    [Google Scholar]
  58. Teli P. Kale V. Vaidya A. Beyond animal models: Revolutionizing neurodegenerative disease modeling using 3D in vitro organoids, microfluidic chips, and bioprinting. Cell Tissue Res. 2023 394 1 75 91 10.1007/s00441‑023‑03821‑2 37572163
    [Google Scholar]
/content/journals/cpd/10.2174/0113816128374254250605070049
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Exploring Neurodegenerative Diseases: Bridging the Gap between in vitro and in vivo Models
Bentham Science Publishers ; https://doi.org/10.2174/0113816128374254250605070049
/content/journals/cpd/10.2174/0113816128374254250605070049
/content/journals/cpd/10.2174/0113816128374254250605070049
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  • Article Type:     Review Article
Keywords: in vitro models, immunological disorders ; Alzheimer’s disease ; Degenerative diseases ; Parkinson’s disease ; in vivo models

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