Parkinson's disease induced pluripotent stem cells with triplication of the α-synuclein locus
Open Access
- 23 August 2011
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Communications
- Vol. 2 (1), 440
- https://doi.org/10.1038/ncomms1453
Abstract
A major barrier to research on Parkinson's disease is inaccessibility of diseased tissue for study. One solution is to derive induced pluripotent stem cells from patients and differentiate them into neurons affected by disease. Triplication of SNCA, encoding α-synuclein, causes a fully penetrant, aggressive form of Parkinson's disease with dementia. α-Synuclein dysfunction is the critical pathogenic event in Parkinson's disease, multiple system atrophy and dementia with Lewy bodies. Here we produce multiple induced pluripotent stem cell lines from an SNCA triplication patient and an unaffected first-degree relative. When these cells are differentiated into midbrain dopaminergic neurons, those from the patient produce double the amount of α-synuclein protein as neurons from the unaffected relative, precisely recapitulating the cause of Parkinson's disease in these individuals. This model represents a new experimental system to identify compounds that reduce levels of α-synuclein, and to investigate the mechanistic basis of neurodegeneration caused by α-synuclein dysfunction.Keywords
This publication has 61 references indexed in Scilit:
- Clinical features, with video documentation, of the original familial lewy body parkinsonism caused by α‐synuclein triplication (Iowa kindred)Movement Disorders, 2011
- Lysosomal dysfunction increases exosome-mediated alpha-synuclein release and transmissionNeurobiology of Disease, 2011
- LRRK2 Mutant iPSC-Derived DA Neurons Demonstrate Increased Susceptibility to Oxidative StressCell Stem Cell, 2011
- Genetic Analysis of Pathways to Parkinson DiseaseNeuron, 2010
- Genetic Animal Models of Parkinson's DiseaseNeuron, 2010
- Technical Challenges in Using Human Induced Pluripotent Stem Cells to Model DiseaseCell Stem Cell, 2009
- Parkinson's Disease Patient-Derived Induced Pluripotent Stem Cells Free of Viral Reprogramming FactorsCell, 2009
- Disease-Specific Induced Pluripotent Stem CellsCell, 2008
- Cell systems and the toxic mechanism(s) of α-synucleinExperimental Neurology, 2007
- Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined FactorsCell, 2006