Advances in iPSC Technology in Neural Disease Modeling, Drug Screening, and Therapy


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Abstract

Neurodegenerative disorders (NDs) including Alzheimer’s Disease, Parkinson’s Disease, Amyotrophic Lateral Sclerosis (ALS), and Huntington's disease are all incurable and can only be managed with drugs for the associated symptoms. Animal models of human illnesses help to advance our understanding of the pathogenic processes of diseases. Understanding the pathogenesis as well as drug screening using appropriate disease models of neurodegenerative diseases (NDs) are vital for identifying novel therapies. Human-derived induced pluripotent stem cell (iPSC) models can be an efficient model to create disease in a dish and thereby can proceed with drug screening and identifying appropriate drugs. This technology has many benefits, including efficient reprogramming and regeneration potential, multidirectional differentiation, and the lack of ethical concerns, which open up new avenues for studying neurological illnesses in greater depth. The review mainly focuses on the use of iPSC technology in neuronal disease modeling, drug screening, and cell therapy.

About the authors

Sihan Dai

Department of Biomedical Engineering, Shantou University

Email: info@benthamscience.net

Linhui Qiu

Department of Biomedical Engineering, Shantou University

Email: info@benthamscience.net

Vishnu Veeraraghavan

Centre of Molecular Medicine and Diagnostics (COMManD), Department of Biochemistry, Saveetha Dental College and Hospitals,, Saveetha Institute of Medical and Technical Sciences, Saveetha University

Email: info@benthamscience.net

Chia-Lin Sheu

Department of Biomedical Engineering, Shantou University

Author for correspondence.
Email: info@benthamscience.net

Ullas Mony

Centre of Molecular Medicine and Diagnostics (COMManD), Department of Biochemistry, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University,

Author for correspondence.
Email: info@benthamscience.net

References

  1. Takahashi K, Tanabe K, Ohnuki M, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 2007; 131(5): 861-72. doi: 10.1016/j.cell.2007.11.019 PMID: 18035408
  2. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006; 126(4): 663-76. doi: 10.1016/j.cell.2006.07.024 PMID: 16904174
  3. Wu Z, Chen J, Ren J, et al. Generation of pig induced pluripotent stem cells with a drug-inducible system. J Mol Cell Biol 2009; 1(1): 46-54. doi: 10.1093/jmcb/mjp003 PMID: 19502222
  4. Chiang CH, Wu WW, Li HY, et al. Enhanced antioxidant capacity of dental pulp-derived iPSC-differentiated hepatocytes and liver regeneration by injectable HGF-releasing hydrogel in fulminant hepatic failure. Cell Transplant 2015; 24(3): 541-59. doi: 10.3727/096368915X686986 PMID: 25668102
  5. Vlahos K, Sourris K, Mayberry R, et al. Generation of iPSC lines from peripheral blood mononuclear cells from 5 healthy adults. Stem Cell Res 2019; 34: 101380. doi: 10.1016/j.scr.2018.101380 PMID: 30605840
  6. Kim Y, Park N, Rim YA, et al. Establishment of a complex skin structure via layered co-culture of keratinocytes and fibroblasts derived from induced pluripotent stem cells. Stem Cell Res Ther 2018; 9(1): 217. doi: 10.1186/s13287-018-0958-2 PMID: 30103800
  7. Li X, Xu R, Tu X, et al. Differentiation of Neural Crest Stem Cells in Response to Matrix Stiffness and TGF-β1 in Vascular Regeneration. Stem Cells Dev 2020; 29(4): 249-56. doi: 10.1089/scd.2019.0161 PMID: 31701817
  8. Shi Y, Inoue H, Wu JC, Yamanaka S. Induced pluripotent stem cell technology: a decade of progress. Nat Rev Drug Discov 2017; 16(2): 115-30. doi: 10.1038/nrd.2016.245 PMID: 27980341
  9. Begley CG, Ellis LM. Raise standards for preclinical cancer research. Nature 2012; 483(7391): 531-3. doi: 10.1038/483531a PMID: 22460880
  10. Paik DT, Chandy M, Wu JC. Patient and Disease–Specific Induced Pluripotent Stem Cells for Discovery of Personalized Cardiovascular Drugs and Therapeutics. Pharmacol Rev 2020; 72(1): 320-42. doi: 10.1124/pr.116.013003 PMID: 31871214
  11. Komor AC, Kim YB, Packer MS, Zuris JA, Liu DR. Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage. Nature 2016; 533(7603): 420-4. doi: 10.1038/nature17946 PMID: 27096365
  12. Dawson TM, Golde TE, Lagier-Tourenne C. Animal models of neurodegenerative diseases. Nat Neurosci 2018; 21(10): 1370-9. doi: 10.1038/s41593-018-0236-8 PMID: 30250265
  13. Doss MX, Sachinidis A. Current challenges of iPSC-based disease modeling and therapeutic implications. Cells 2019; 8(5): 403. doi: 10.3390/cells8050403 PMID: 31052294
  14. Zhao M, Nakada Y, Wei Y, et al. Cyclin D2 overexpression enhances the efficacy of human induced pluripotent stem cell–derived cardiomyocytes for myocardial repair in a swine model of myocardial infarction. Circulation 2021; 144(3): 210-28. doi: 10.1161/CIRCULATIONAHA.120.049497 PMID: 33951921
  15. Kimbrel EA, Lanza R. Current status of pluripotent stem cells: moving the first therapies to the clinic. Nat Rev Drug Discov 2015; 14(10): 681-92. doi: 10.1038/nrd4738 PMID: 26391880
  16. Scudellari M. How iPS cells changed the world. Nature 2016; 534(7607): 310-2. doi: 10.1038/534310a PMID: 27306170
  17. Onos KD, Sukoff Rizzo SJ, Howell GR, Sasner M. Toward more predictive genetic mouse models of Alzheimer’s disease. Brain Res Bull 2016; 122: 1-11. doi: 10.1016/j.brainresbull.2015.12.003 PMID: 26708939
  18. Penney J, Ralvenius WT, Tsai LH. Modeling Alzheimer’s disease with iPSC-derived brain cells. Mol Psychiatry 2020; 25(1): 148-67. doi: 10.1038/s41380-019-0468-3 PMID: 31391546
  19. Tam KY, Ju Y. Pathological mechanisms and therapeutic strategies for Alzheimer’s disease. Neural Regen Res 2022; 17(3): 543-9. doi: 10.4103/1673-5374.320970 PMID: 34380884
  20. Scheltens P, De Strooper B, Kivipelto M, et al. Alzheimer’s disease. Lancet 2021; 397(10284): 1577-90. doi: 10.1016/S0140-6736(20)32205-4 PMID: 33667416
  21. William F Goure GAK. Targeting the proper amyloid-beta neuronal toxins: A path forward for Alzheimer’s disease immuno therapeutics. Alz Res Therapy 2014; 6: 42.
  22. Busche MA, Wegmann S, Dujardin S, et al. Tau impairs neural circuits, dominating amyloid-β effects, in Alzheimer models in vivo. Nat Neurosci 2019; 22(1): 57-64. doi: 10.1038/s41593-018-0289-8 PMID: 30559471
  23. Goedert M. Alzheimer’s and Parkinson’s diseases: The prion concept in relation to assembled Aβ, tau, and α-synuclein. Science 2015; 349(6248): 1255555. doi: 10.1126/science.1255555 PMID: 26250687
  24. Jeong S. Molecular and cellular basis of neurodegeneration in Alzheimer’s Disease. Mol Cells 2017; 40(9): 613-20. PMID: 28927263
  25. Goetzl EJ, Kapogiannis D, Schwartz JB, et al. Decreased synaptic proteins in neuronal exosomes of frontotemporal dementia and Alzheimer’s disease. FASEB J 2016; 30(12): 4141-8. doi: 10.1096/fj.201600816R PMID: 27601437
  26. Duncan T, Valenzuela M. Alzheimer’s disease, dementia, and stem cell therapy. Stem Cell Res Ther 2017; 8(1): 111. doi: 10.1186/s13287-017-0567-5 PMID: 28494803
  27. Jonsson T, Stefansson H, Steinberg S, et al. Variant of TREM2 associated with the risk of Alzheimer’s disease. N Engl J Med 2013; 368(2): 107-16. doi: 10.1056/NEJMoa1211103 PMID: 23150908
  28. Lin YT, Seo J, Gao F, et al. APOE4 causes widespread molecular and cellular alterations associated with alzheimer’s disease phenotypes in human ipsc-derived brain cell types. Neuron 2018; 98(6): 1141-1154.e7. doi: 10.1016/j.neuron.2018.05.008 PMID: 29861287
  29. Kunkle BW, et al. Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates A beta, tau, immunity and lipid processing. Nat Genet 2019; 51(9): 1423-4. doi: 10.1038/s41588-019-0495-7 PMID: 31417202
  30. Huang K, Marcora E, Pimenova AA, et al. A common haplotype lowers PU.1 expression in myeloid cells and delays onset of Alzheimer’s disease. Nat Neurosci 2017; 20(8): 1052-61. doi: 10.1038/nn.4587 PMID: 28628103
  31. Kondo T, Asai M, Tsukita K, et al. Modeling Alzheimer’s disease with iPSCs reveals stress phenotypes associated with intracellular Aβ and differential drug responsiveness. Cell Stem Cell 2013; 12(4): 487-96. doi: 10.1016/j.stem.2013.01.009 PMID: 23434393
  32. Gonzalez C, Armijo E, Bravo-Alegria J, Becerra-Calixto A, Mays CE, Soto C. Modeling amyloid beta and tau pathology in human cerebral organoids. Mol Psychiatry 2018; 23(12): 2363-74. doi: 10.1038/s41380-018-0229-8 PMID: 30171212
  33. Park JC, Jang SY, Lee D, et al. A logical network-based drug-screening platform for Alzheimer’s disease representing pathological features of human brain organoids. Nat Commun 2021; 12(1): 280. doi: 10.1038/s41467-020-20440-5 PMID: 33436582
  34. Chang KH, Lee-Chen GJ, Huang CC, et al. Modeling Alzheimer’s disease by induced pluripotent stem cells carrying APP D678H mutation. Mol Neurobiol 2019; 56(6): 3972-83. doi: 10.1007/s12035-018-1336-x PMID: 30238389
  35. Ochalek A, Mihalik B, Avci HX, et al. Neurons derived from sporadic Alzheimer’s disease iPSCs reveal elevated TAU hyperphosphorylation, increased amyloid levels, and GSK3B activation. Alzheimers Res Ther 2017; 9(1): 90. doi: 10.1186/s13195-017-0317-z PMID: 29191219
  36. van der Kant R, Langness VF, Herrera CM, et al. Cholesterol metabolism is a druggable axis that independently regulates Tau and amyloid-β in iPSC-derived Alzheimer’s disease neurons. Cell Stem Cell 2019; 24(3): 363-375.e9. doi: 10.1016/j.stem.2018.12.013 PMID: 30686764
  37. Kondo T, Imamura K, Funayama M, et al. iPSC-based compound screening and in vitro trials identify a synergistic anti-amyloid β combination for Alzheimer’s Disease. Cell Rep 2017; 21(8): 2304-12. doi: 10.1016/j.celrep.2017.10.109 PMID: 29166618
  38. Vuidel A, Cousin L, Weykopf B, et al. High-content phenotyping of Parkinson’s disease patient stem cell-derived midbrain dopaminergic neurons using machine learning classification. Stem Cell Reports 2022; 17(10): 2349-64. doi: 10.1016/j.stemcr.2022.09.001 PMID: 36179692
  39. Du F, Yu Q, Chen A, Chen D, Yan SS. Astrocytes attenuate mitochondrial dysfunctions in human dopaminergic neurons derived from iPSC. Stem Cell Reports 2018; 10(2): 366-74. doi: 10.1016/j.stemcr.2017.12.021 PMID: 29396183
  40. Magistrelli L, Ferrari M, Furgiuele A, et al. Polymorphisms of dopamine receptor genes and Parkinson’s Disease: Clinical relevance and future perspectives. Int J Mol Sci 2021; 22(7): 3781. doi: 10.3390/ijms22073781 PMID: 33917417
  41. Lee D, Dallapiazza R, De Vloo P, Lozano A. Current surgical treatments for Parkinson’s disease and potential therapeutic targets. Neural Regen Res 2018; 13(8): 1342-5. doi: 10.4103/1673-5374.235220 PMID: 30106037
  42. Jaiswal MK. Riluzole and edaravone: A tale of two amyotrophic lateral sclerosis drugs. Med Res Rev 2019; 39(2): 733-48. doi: 10.1002/med.21528 PMID: 30101496
  43. Osaki T, Uzel SGM, Kamm RD. Microphysiological 3D model of amyotrophic lateral sclerosis (ALS) from human iPS-derived muscle cells and optogenetic motor neurons. Sci Adv 2018; 4(10): eaat5847. doi: 10.1126/sciadv.aat5847 PMID: 30324134
  44. Okano H, Yasuda D, Fujimori K, Morimoto S, Takahashi S. Ropinirole, a new ALS drug candidate developed using iPSCs. Trends Pharmacol Sci 2020; 41(2): 99-109. doi: 10.1016/j.tips.2019.12.002 PMID: 31926602
  45. Lopez-Gonzalez R, Lu Y, Gendron TF, et al. Poly(GR) in C9ORF72 -related als/ftd compromises mitochondrial function and increases oxidative stress and dna damage in ipsc-derived motor neurons. Neuron 2016; 92(2): 383-91. doi: 10.1016/j.neuron.2016.09.015 PMID: 27720481
  46. Maezawa I, Jin LW. Rett syndrome microglia damage dendrites and synapses by the elevated release of glutamate. J Neurosci 2010; 30(15): 5346-56. doi: 10.1523/JNEUROSCI.5966-09.2010 PMID: 20392956
  47. Rodrigues FB, Duarte GS, Costa J, Ferreira JJ, Wild EJ. Tetrabenazine versus deutetrabenazine for huntington’s disease: twins or distant cousins? Mov Disord Clin Pract (Hoboken) 2017; 4(4): 582-5. doi: 10.1002/mdc3.12483 PMID: 28920068
  48. Kordasiewicz HB, Stanek LM, Wancewicz EV, et al. Sustained therapeutic reversal of Huntington’s disease by transient repression of huntingtin synthesis. Neuron 2012; 74(6): 1031-44. doi: 10.1016/j.neuron.2012.05.009 PMID: 22726834
  49. Park HJ, Jeon J, Choi J, et al. Human iPSC‐derived neural precursor cells differentiate into multiple cell types to delay disease progression following transplantation into YAC128 Huntington’s disease mouse model. Cell Prolif 2021; 54(8): e13082. doi: 10.1111/cpr.13082 PMID: 34152047
  50. Hasselmann J, Coburn MA, England W, et al. Development of a chimeric model to study and manipulate human microglia In Vivo. Neuron 2019; 103(6): 1016-1033.e10. doi: 10.1016/j.neuron.2019.07.002 PMID: 31375314
  51. Day JO, Mullin S. The genetics of Parkinson’s Disease and implications for clinical practice. Genes 2021; 12(7): 1006. doi: 10.3390/genes12071006 PMID: 34208795
  52. Pierzchlińska A, Droździk M, Białecka M. A possible role for HMG-CoA reductase inhibitors and its association with HMGCR Genetic variation in Parkinson’s Disease. Int J Mol Sci 2021; 22(22): 12198. doi: 10.3390/ijms222212198 PMID: 34830081
  53. Palermo G, Giannoni S, Bellini G, Siciliano G, Ceravolo R. Dopamine transporter imaging, current status of a potential biomarker: A comprehensive review. Int J Mol Sci 2021; 22(20): 11234. doi: 10.3390/ijms222011234 PMID: 34681899
  54. Pajares M, I Rojo A, Manda G, Boscá L, Cuadrado A. Inflammation in Parkinson’s Disease: Mechanisms and therapeutic implications. Cells 2020; 9(7): 1687. doi: 10.3390/cells9071687 PMID: 32674367
  55. Yang P, Pavlovic D, Waldvogel H, et al. String vessel formation is increased in the brain of Parkinson Disease. J Parkinsons Dis 2015; 5(4): 821-36. doi: 10.3233/JPD-140454 PMID: 26444086
  56. Reynolds RH, Botía J, Nalls MA, et al. Moving beyond neurons: the role of cell type-specific gene regulation in Parkinson’s disease heritability. NPJ Parkinsons Dis 2019; 5(1): 6. doi: 10.1038/s41531-019-0076-6 PMID: 31016231
  57. Booth HDE, Hirst WD, Wade-Martins R. The role of astrocyte dysfunction in Parkinson’s disease pathogenesis. Trends Neurosci 2017; 40(6): 358-70. doi: 10.1016/j.tins.2017.04.001 PMID: 28527591
  58. Pons-Espinal M, Blasco-Agell L, Consiglio A. Dissecting the non-neuronal cell contribution to Parkinson’s disease pathogenesis using induced pluripotent stem cells. Cell Mol Life Sci 2021; 78(5): 2081-94. doi: 10.1007/s00018-020-03700-x PMID: 33210214
  59. Schneider JS, Kortagere S. Current concepts in treating mild cognitive impairment in Parkinson’s disease. Neuropharmacology 2022; 203: 108880. doi: 10.1016/j.neuropharm.2021.108880 PMID: 34774549
  60. Osman M, Ryterska A, Karimi K, et al. The effects of dopaminergic medication on dynamic decision making in Parkinson’s disease. Neuropsychologia 2014; 53: 157-64. doi: 10.1016/j.neuropsychologia.2013.10.024 PMID: 24269857
  61. Stoddard-Bennett T, Reijo Pera R. Treatment of Parkinson’s Disease through personalized medicine and induced pluripotent stem cells. Cells 2019; 8(1): 26. doi: 10.3390/cells8010026 PMID: 30621042
  62. Brown RH, Al-Chalabi A. Amyotrophic lateral sclerosis. N Engl J Med 2017; 377(2): 162-72. doi: 10.1056/NEJMra1603471 PMID: 28700839
  63. Csobonyeiova M, Polak S, Nicodemou A, Danisovic L. Induced pluripotent stem cells in modeling and cell-based therapy of amyotrophic lateral sclerosis. J Physiol Pharmacol 2017; 68(5): 649-57. PMID: 29375039
  64. Wobst HJ, Mack KL, Brown DG, Brandon NJ, Shorter J. The clinical trial landscape in amyotrophic lateral sclerosis—Past, present, and future. Med Res Rev 2020; 40(4): 1352-84. doi: 10.1002/med.21661 PMID: 32043626
  65. Zarei S, Carr K, Reiley L, et al. A comprehensive review of amyotrophic lateral sclerosis. Surg Neurol Int 2015; 6(1): 171. doi: 10.4103/2152-7806.169561 PMID: 26629397
  66. Sever B, Ciftci H, DeMirci H, et al. Comprehensive research on past and future therapeutic strategies devoted to treatment of amyotrophic lateral sclerosis. Int J Mol Sci 2022; 23(5): 2400. doi: 10.3390/ijms23052400 PMID: 35269543
  67. Jankovic M, Novakovic I, Gamil Anwar Dawod P, et al. Current concepts on genetic aspects of mitochondrial dysfunction in amyotrophic lateral sclerosis. Int J Mol Sci 2021; 22(18): 9832. doi: 10.3390/ijms22189832 PMID: 34575995
  68. Devlin AC, Burr K, Borooah S, et al. Human iPSC-derived motoneurons harbouring TARDBP or C9ORF72 ALS mutations are dysfunctional despite maintaining viability. Nat Commun 2015; 6(1): 5999. doi: 10.1038/ncomms6999 PMID: 25580746
  69. Steinbeck JA, Jaiswal MK, Calder EL, et al. Functional connectivity under optogenetic control allows modeling of human neuromuscular disease. Cell Stem Cell 2016; 18(1): 134-43. doi: 10.1016/j.stem.2015.10.002 PMID: 26549107
  70. Pradat PF, Bruneteau G, Gonzalez de Aguilar JL, et al. Muscle Nogo-a expression is a prognostic marker in lower motor neuron syndromes. Ann Neurol 2007; 62(1): 15-20. doi: 10.1002/ana.21122 PMID: 17455292
  71. Lin CY, et al. Extracellular Pgk1 enhances neurite outgrowth of motoneurons through Nogo66/NgR-independent targeting of NogoA. eLife 2019; 8.
  72. Chang CY, Ting HC, Liu CA, et al. Induced Pluripotent Stem Cell (iPSC)-based neurodegenerative disease models for phenotype recapitulation and drug screening. Molecules 2020; 25(8): 2000. doi: 10.3390/molecules25082000 PMID: 32344649
  73. López-Cortés A, Echeverría-Garcés G, Ramos-Medina MJ. Molecular pathogenesis and new therapeutic dimensions for spinal muscular atrophy. Biology 2022; 11(6): 894. doi: 10.3390/biology11060894 PMID: 35741415
  74. Ogino S, Wilson RB. Spinal muscular atrophy: molecular genetics and diagnostics. Expert Rev Mol Diagn 2004; 4(1): 15-29. doi: 10.1586/14737159.4.1.15 PMID: 14711346
  75. Feldkötter M, Schwarzer V, Wirth R, Wienker TF, Wirth B. Quantitative analyses of SMN1 and SMN2 based on real-time lightCycler PCR: fast and highly reliable carrier testing and prediction of severity of spinal muscular atrophy. Am J Hum Genet 2002; 70(2): 358-68. doi: 10.1086/338627 PMID: 11791208
  76. Zhou M, Hu Z, Qiu L, et al. Seamless genetic conversion of SMN2 to SMN1 via CRISPR/Cpf1 and single-stranded oligodeoxynucleotides in spinal muscular atrophy patient-specific induced pluripotent stem cells. Hum Gene Ther 2018; 29(11): 1252-63. doi: 10.1089/hum.2017.255 PMID: 29598153
  77. Coovert D, Le TT, McAndrew PE, et al. The survival motor neuron protein in spinal muscular atrophy. Hum Mol Genet 1997; 6(8): 1205-14. doi: 10.1093/hmg/6.8.1205 PMID: 9259265
  78. Lorson CL, Hahnen E, Androphy EJ, Wirth B. A single nucleotide in the SMN gene regulates splicing and is responsible for spinal muscular atrophy. Proc Natl Acad Sci USA 1999; 96(11): 6307-11. doi: 10.1073/pnas.96.11.6307 PMID: 10339583
  79. Hauser S, Schuster S, Heuten E, et al. Comparative transcriptional profiling of motor neuron disorder-associated genes in various human cell culture models. Front Cell Dev Biol 2020; 8: 544043. doi: 10.3389/fcell.2020.544043 PMID: 33072739
  80. Andoh-Noda T, Inouye MO, Miyake K, Kubota T, Okano H, Akamatsu W. Modeling rett syndrome using human induced pluripotent stem cells. CNS Neurol Disord Drug Targets 2016; 15(5): 544-50. doi: 10.2174/1871527315666160413120156 PMID: 27071793
  81. Marchetto MCN, Carromeu C, Acab A, et al. A model for neural development and treatment of Rett syndrome using human induced pluripotent stem cells. Cell 2010; 143(4): 527-39. doi: 10.1016/j.cell.2010.10.016 PMID: 21074045
  82. Bourgeron T. From the genetic architecture to synaptic plasticity in autism spectrum disorder. Nat Rev Neurosci 2015; 16(9): 551-63. doi: 10.1038/nrn3992 PMID: 26289574
  83. Avior Y, Sagi I, Benvenisty N. Pluripotent stem cells in disease modelling and drug discovery. Nat Rev Mol Cell Biol 2016; 17(3): 170-82. doi: 10.1038/nrm.2015.27 PMID: 26818440
  84. Barral S, Kurian MA. Utility of induced pluripotent stem cells for the study and treatment of genetic diseases: focus on childhood neurological disorders. Front Mol Neurosci 2016; 9: 78. doi: 10.3389/fnmol.2016.00078 PMID: 27656126
  85. Di Giorgio FP, Boulting GL, Bobrowicz S, Eggan KC. Human embryonic stem cell-derived motor neurons are sensitive to the toxic effect of glial cells carrying an ALS-causing mutation. Cell Stem Cell 2008; 3(6): 637-48. doi: 10.1016/j.stem.2008.09.017 PMID: 19041780
  86. Di Giorgio FP, Carrasco MA, Siao MC, Maniatis T, Eggan K. Non–cell autonomous effect of glia on motor neurons in an embryonic stem cell–based ALS model. Nat Neurosci 2007; 10(5): 608-14. doi: 10.1038/nn1885 PMID: 17435754
  87. Lindvall O, Kokaia Z. Stem cells for the treatment of neurological disorders. Nature 2006; 441(7097): 1094-6. doi: 10.1038/nature04960 PMID: 16810245
  88. Chiaradia I, Lancaster MA. Brain organoids for the study of human neurobiology at the interface of in vitro and in vivo. Nat Neurosci 2020; 23(12): 1496-508. doi: 10.1038/s41593-020-00730-3 PMID: 33139941
  89. Yoshida S, Miwa H, Kawachi T, Kume S, Takahashi K. Generation of intestinal organoids derived from human pluripotent stem cells for drug testing. Sci Rep 2020; 10(1): 5989. doi: 10.1038/s41598-020-63151-z PMID: 32249832
  90. Ebert AD, Yu J, Rose FF Jr, et al. Induced pluripotent stem cells from a spinal muscular atrophy patient. Nature 2009; 457(7227): 277-80. doi: 10.1038/nature07677 PMID: 19098894
  91. Sareen D, Ebert AD, Heins BM, McGivern JV, Ornelas L, Svendsen CN. Inhibition of apoptosis blocks human motor neuron cell death in a stem cell model of spinal muscular atrophy. PLoS One 2012; 7(6): e39113. doi: 10.1371/journal.pone.0039113 PMID: 22723941
  92. Wang ZB, Zhang X, Li XJ. Recapitulation of spinal motor neuron-specific disease phenotypes in a human cell model of spinal muscular atrophy. Cell Res 2013; 23(3): 378-93. doi: 10.1038/cr.2012.166 PMID: 23208423
  93. Ohuchi K, Funato M, Kato Z, et al. Established stem cell model of spinal muscular atrophy is applicable in the evaluation of the efficacy of thyrotropin-releasing hormone analog. Stem Cells Transl Med 2016; 5(2): 152-63. doi: 10.5966/sctm.2015-0059 PMID: 26683872
  94. Naryshkin NA, Weetall M, Dakka A, et al. SMN2 splicing modifiers improve motor function and longevity in mice with spinal muscular atrophy. Science 2014; 345(6197): 688-93. doi: 10.1126/science.1250127 PMID: 25104390
  95. Porensky PN, Mitrpant C, McGovern VL, et al. A single administration of morpholino antisense oligomer rescues spinal muscular atrophy in mouse. Hum Mol Genet 2012; 21(7): 1625-38. doi: 10.1093/hmg/ddr600 PMID: 22186025
  96. Zanetta C, Nizzardo M, Simone C, et al. Molecular therapeutic strategies for spinal muscular atrophies: current and future clinical trials. Clin Ther 2014; 36(1): 128-40. doi: 10.1016/j.clinthera.2013.11.006 PMID: 24360800
  97. Zanetta C, Riboldi G, Nizzardo M, et al. Molecular, genetic and stem cell‐mediated therapeutic strategies for spinal muscular atrophy (SMA). J Cell Mol Med 2014; 18(2): 187-96. doi: 10.1111/jcmm.12224 PMID: 24400925
  98. Hua Y, Sahashi K, Rigo F, et al. Peripheral SMN restoration is essential for long-term rescue of a severe spinal muscular atrophy mouse model. Nature 2011; 478(7367): 123-6. doi: 10.1038/nature10485 PMID: 21979052
  99. Nizzardo M, Simone C, Salani S, et al. Effect of combined systemic and local morpholino treatment on the spinal muscular atrophy Δ7 mouse model phenotype. Clin Ther 2014; 36(3): 340-356.e5. doi: 10.1016/j.clinthera.2014.02.004 PMID: 24636820
  100. Nizzardo M, Simone C, Dametti S, et al. Spinal muscular atrophy phenotype is ameliorated in human motor neurons by SMN increase via different novel RNA therapeutic approaches. Sci Rep 2015; 5(1): 11746. doi: 10.1038/srep11746 PMID: 26123042
  101. Chaytow H, Faller KME, Huang YT, Gillingwater TH. Spinal muscular atrophy: From approved therapies to future therapeutic targets for personalized medicine. Cell Rep Med 2021; 2(7): 100346. doi: 10.1016/j.xcrm.2021.100346 PMID: 34337562
  102. Ross CA, Poirier MA. Protein aggregation and neurodegenerative disease. Nat Med 2004; 10(S7) (Suppl.): S10-7. doi: 10.1038/nm1066 PMID: 15272267
  103. Soto C, Pritzkow S. Protein misfolding, aggregation, and conformational strains in neurodegenerative diseases. Nat Neurosci 2018; 21(10): 1332-40. doi: 10.1038/s41593-018-0235-9 PMID: 30250260
  104. Mohandas E, Rajmohan V. Frontotemporal dementia: An updated overview. Indian J Psychiatry 51(s1): 65-9. PMID: 21416021
  105. Bocchetta M, Malpetti M, Todd EG, Rowe JB, Rohrer JD. Looking beneath the surface: the importance of subcortical structures in frontotemporal dementia. Brain Commun 2021; 3(3): fcab158. doi: 10.1093/braincomms/fcab158 PMID: 34458729
  106. Nakamura M, Shiozawa S, Tsuboi D, et al. Pathological progression induced by the frontotemporal dementia-associated r406w tau mutation in patient-derived iPSCs. Stem Cell Reports 2019; 13(4): 684-99. doi: 10.1016/j.stemcr.2019.08.011 PMID: 31543469
  107. Kühn R, Mahajan A, Canoll P, Hargus G. Human induced pluripotent stem cell models of frontotemporal dementia with tau pathology. Front Cell Dev Biol 2021; 9: 766773. doi: 10.3389/fcell.2021.766773 PMID: 34858989
  108. Bocchetta M, Gordon E, Manning E, et al. Detailed volumetric analysis of the hypothalamus in behavioral variant frontotemporal dementia. J Neurol 2015; 262(12): 2635-42. doi: 10.1007/s00415-015-7885-2 PMID: 26338813
  109. Honson NS, Kuret J. Tau aggregation and toxicity in tauopathic neurodegenerative diseases. J Alzheimers Dis 2008; 14(4): 417-22. doi: 10.3233/JAD-2008-14409 PMID: 18688092
  110. Liu F, Gong CX. Tau exon 10 alternative splicing and tauopathies. Mol Neurodegener 2008; 3(1): 8. doi: 10.1186/1750-1326-3-8 PMID: 18616804
  111. Camp JG, Badsha F, Florio M, et al. Human cerebral organoids recapitulate gene expression programs of fetal neocortex development. Proc Natl Acad Sci USA 2015; 112(51): 15672-7. doi: 10.1073/pnas.1520760112 PMID: 26644564
  112. Imamura K, Sahara N, Kanaan NM, et al. Calcium dysregulation contributes to neurodegeneration in FTLD patient iPSC-derived neurons. Sci Rep 2016; 6(1): 34904. doi: 10.1038/srep34904 PMID: 27721502
  113. Medda X, Mertens L, Versweyveld S, et al. Development of a scalable, high-throughput-compatible assay to detect tau aggregates using ipsc-derived cortical neurons maintained in a three-dimensional culture format. SLAS Discov 2016; 21(8): 804-15. doi: 10.1177/1087057116638029 PMID: 26984927
  114. Silva MC, Ferguson FM, Cai Q, et al. Targeted degradation of aberrant tau in frontotemporal dementia patient-derived neuronal cell models. eLife 2019; 8: e45457. doi: 10.7554/eLife.45457 PMID: 30907729
  115. Krishnan G, Raitcheva D, Bartlett D, et al. Poly(GR) and poly(GA) in cerebrospinal fluid as potential biomarkers for C9ORF72-ALS/FTD. Nat Commun 2022; 13(1): 2799. doi: 10.1038/s41467-022-30387-4 PMID: 35589711
  116. Valdez C, Wong YC, Schwake M, Bu G, Wszolek ZK, Krainc D. Progranulin-mediated deficiency of cathepsin D results in FTD and NCL-like phenotypes in neurons derived from FTD patients. Hum Mol Genet 2017; 26(24): 4861-72. doi: 10.1093/hmg/ddx364 PMID: 29036611
  117. Dafinca R, Scaber J, Ababneh N, et al. C9orf72 hexanucleotide expansions are associated with altered endoplasmic reticulum calcium homeostasis and stress granule formation in induced pluripotent stem cell-derived neurons from patients with amyotrophic lateral sclerosis and frontotemporal dementia. Stem Cells 2016; 34(8): 2063-78. doi: 10.1002/stem.2388 PMID: 27097283
  118. Ehrlich M, Hallmann AL, Reinhardt P, et al. Distinct neurodegenerative changes in an induced pluripotent stem cell model of frontotemporal dementia linked to mutant TAU protein. Stem Cell Reports 2015; 5(1): 83-96. doi: 10.1016/j.stemcr.2015.06.001 PMID: 26143746
  119. Melamed Z, López-Erauskin J, Baughn MW, et al. Premature polyadenylation-mediated loss of stathmin-2 is a hallmark of TDP-43-dependent neurodegeneration. Nat Neurosci 2019; 22(2): 180-90. doi: 10.1038/s41593-018-0293-z PMID: 30643298
  120. Kim M, Kim HJ, Koh W, et al. Modeling of frontotemporal dementia using iPSC technology. Int J Mol Sci 2020; 21(15): 5319. doi: 10.3390/ijms21155319 PMID: 32727073
  121. López-Pousa S, Calvó-Perxas L, Lejarreta S, et al. Use of antidementia drugs in frontotemporal lobar degeneration. Am J Alzheimers Dis Other Demen 2012; 27(4): 260-6. doi: 10.1177/1533317512447887 PMID: 22605780
  122. Chen SD, Li HQ, Cui M, Dong Q, Yu JT. Pluripotent stem cells for neurodegenerative disease modeling: an expert view on their value to drug discovery. Expert Opin Drug Discov 2020; 15(9): 1081-94. doi: 10.1080/17460441.2020.1767579 PMID: 32425128
  123. Huber N, Korhonen S, Hoffmann D, et al. Deficient neurotransmitter systems and synaptic function in frontotemporal lobar degeneration—Insights into disease mechanisms and current therapeutic approaches. Mol Psychiatry 2022; 27(3): 1300-9. doi: 10.1038/s41380-021-01384-8 PMID: 34799692
  124. Haenseler W, Rajendran L. Concise review: Modeling neurodegenerative diseases with human pluripotent stem cell-derived microglia. Stem Cells 2019; 37(6): 724-30. doi: 10.1002/stem.2995 PMID: 30801863
  125. Chen X, Han X, Blanchi B, et al. Graded and pan-neural disease phenotypes of Rett Syndrome linked with dosage of functional MeCP2. Protein Cell 2021; 12(8): 639-52. doi: 10.1007/s13238-020-00773-z PMID: 32851591
  126. Gomes AR, Fernandes TG, Cabral JMS, Diogo MM. Modeling rett syndrome with human pluripotent stem cells: Mechanistic outcomes and future clinical perspectives. Int J Mol Sci 2021; 22(7): 3751. doi: 10.3390/ijms22073751 PMID: 33916879
  127. Smirnov K, Stroganova T, Molholm S, Sysoeva O. Reviewing evidence for the relationship of EEG abnormalities and RTT phenotype paralleled by insights from animal studies. Int J Mol Sci 2021; 22(10): 5308. doi: 10.3390/ijms22105308 PMID: 34069993
  128. Leonard H, Gold W, Samaco R, Sahin M, Benke T, Downs J. Improving clinical trial readiness to accelerate development of new therapeutics for Rett syndrome. Orphanet J Rare Dis 2022; 17(1): 108. doi: 10.1186/s13023-022-02240-w PMID: 35246185
  129. Cheffer A, Flitsch LJ, Krutenko T, et al. Human stem cell-based models for studying autism spectrum disorder-related neuronal dysfunction. Mol Autism 2020; 11(1): 99. doi: 10.1186/s13229-020-00383-w PMID: 33308283
  130. Balachandar V, Dhivya V, Gomathi M, Mohanadevi S, Venkatesh B, Geetha B. A review of Rett syndrome (RTT) with induced pluripotent stem cells. Stem Cell Investig 2016; 3: 52. doi: 10.21037/sci.2016.09.05 PMID: 27777941
  131. Gomathi M, Padmapriya S, Balachandar V. Drug studies on Rett Syndrome: From bench to bedside. J Autism Dev Disord 2020; 50(8): 2740-64. doi: 10.1007/s10803-020-04381-y PMID: 32016693
  132. Caron NS, Wright GEB, Hayden MR. Huntington Disease. GeneReviewsSeattle, WA 1993.
  133. Roos RAC. Huntington’s disease: a clinical review. Orphanet J Rare Dis 2010; 5(1): 40. doi: 10.1186/1750-1172-5-40 PMID: 21171977
  134. MacDonald M. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington’s disease chromosomes. Cell 1993; 72(6): 971-83. doi: 10.1016/0092-8674(93)90585-E PMID: 8458085
  135. Ross CA, Tabrizi SJ. Huntington’s disease: from molecular pathogenesis to clinical treatment. Lancet Neurol 2011; 10(1): 83-98. doi: 10.1016/S1474-4422(10)70245-3 PMID: 21163446
  136. Conforti P, et al. Faulty neuronal determination and cell polarization are reverted by modulating HD early phenotypes. Proc Natl Acad Sci USA 2018; 115(9): E2148-8. PMID: 29463700
  137. Csobonyeiova M, Polák Š. Recent overview of the use of iPSCs Huntington's Disease modeling and therapy. Int J Mol Sci 2020; 21(6): 2239. doi: 10.3390/ijms21062239 PMID: 32213859
  138. Bachoud-Lévi AC, Ferreira J, Massart R, et al. International guidelines for the treatment of Huntington’s Disease. Front Neurol 2019; 10: 710. doi: 10.3389/fneur.2019.00710 PMID: 31333565
  139. Kaplan A, Stockwell BR. Therapeutic approaches to preventing cell death in Huntington disease. Prog Neurobiol 2012; 99(3): 262-80. doi: 10.1016/j.pneurobio.2012.08.004 PMID: 22967354
  140. Coppen EM, Roos RAC. Current pharmacological approaches to reduce chorea in Huntington’s Disease. Drugs 2017; 77(1): 29-46. doi: 10.1007/s40265-016-0670-4 PMID: 27988871
  141. Safety, tolerability, and efficacy of PBT2 in Huntington’s disease: a phase 2, randomised, double-blind, placebo-controlled trial. Lancet Neurol 2015; 14(1): 39-47. doi: 10.1016/S1474-4422(14)70262-5 PMID: 25467848
  142. Jeon I, Lee N, Li JY, et al. Neuronal properties, in vivo effects, and pathology of a Huntington’s disease patient-derived induced pluripotent stem cells. Stem Cells 2012; 30(9): 2054-62. doi: 10.1002/stem.1135 PMID: 22628015
  143. La Spada AR, Weydt P, Pineda VV. Huntington’s Disease Pathogenesis: Mechanisms and Pathways.Neurobiology of Huntington’s Disease: Applications to Drug Discovery. CRC Press,Taylor and FrancisBoca Raton, FL 2011. PMID: 21882412
  144. Ward JM, La Spada AR. The expanding world of stem cell modeling of Huntington’s disease: creating tools with a promising future. Genome Med 2012; 4(8): 68. doi: 10.1186/gm369 PMID: 22943447

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