TY - JOUR
T1 - Human-induced pluripotent stem cells
T2 - Potential for neurodegenerative diseases
AU - Ross, Christopher A.
AU - Akimov, Sergey S.
PY - 2014/9
Y1 - 2014/9
N2 - The cell biology of human neurodegenerative diseases has been difficult to study till recently. The development of human induced pluripotent stem cell (iPSC) models has greatly enhanced our ability to model disease in human cells. Methods have recently been improved, including increasing reprogramming efficiency, introducing non-viral and non-integrating methods of cell reprogramming, and using novel gene editing techniques for generating genetically corrected lines from patient-derived iPSCs, or for generating mutations in control cell lines. In this review, we highlight accomplishments made using iPSC models to study neurodegenerative disorders such as Huntington's disease, Parkinson's disease, Amyotrophic Lateral Sclerosis, Fronto-Temporal Dementia, Alzheimer's disease, Spinomuscular Atrophy and other polyglutamine diseases. We review disease-related phenotypes shown in patient-derived iPSCs differentiated to relevant neural subtypes, often with stressors or cell "aging", to enhance disease-specific phenotypes. We also discuss prospects for the future of using ofiPSCmodelsofneurodegenerative disorders, includingscreeningandtesting of therapeutic compounds, and possibly of cell transplantation in regenerative medicine. The new iPSC models have the potential to greatly enhance our understanding of pathogenesis and to facilitate the development of novel therapeutics.
AB - The cell biology of human neurodegenerative diseases has been difficult to study till recently. The development of human induced pluripotent stem cell (iPSC) models has greatly enhanced our ability to model disease in human cells. Methods have recently been improved, including increasing reprogramming efficiency, introducing non-viral and non-integrating methods of cell reprogramming, and using novel gene editing techniques for generating genetically corrected lines from patient-derived iPSCs, or for generating mutations in control cell lines. In this review, we highlight accomplishments made using iPSC models to study neurodegenerative disorders such as Huntington's disease, Parkinson's disease, Amyotrophic Lateral Sclerosis, Fronto-Temporal Dementia, Alzheimer's disease, Spinomuscular Atrophy and other polyglutamine diseases. We review disease-related phenotypes shown in patient-derived iPSCs differentiated to relevant neural subtypes, often with stressors or cell "aging", to enhance disease-specific phenotypes. We also discuss prospects for the future of using ofiPSCmodelsofneurodegenerative disorders, includingscreeningandtesting of therapeutic compounds, and possibly of cell transplantation in regenerative medicine. The new iPSC models have the potential to greatly enhance our understanding of pathogenesis and to facilitate the development of novel therapeutics.
UR - http://www.scopus.com/inward/record.url?scp=84906829737&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84906829737&partnerID=8YFLogxK
U2 - 10.1093/hmg/ddu204
DO - 10.1093/hmg/ddu204
M3 - Article
C2 - 24824217
AN - SCOPUS:84906829737
SN - 0964-6906
VL - 23
SP - R17-R26
JO - Human molecular genetics
JF - Human molecular genetics
IS - R1
ER -