Devine, MJ and Ryten, M and Vodicka, P and Thomson, AJ and Burdon, T and Houlden, H and Cavaleri, F and Nagano, M and Drummond, NJ and Taanman, JW and Schapira, AH and Gwinn, K and Hardy, J and Lewis, PA and Kunath, T (2011) Parkinson's disease induced pluripotent stem cells with triplication of the alpha-synuclein locus. NAT COMMUN , 2 , Article 440. 10.1038/ncomms1453.
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 alpha-synuclein, causes a fully penetrant, aggressive form of Parkinson's disease with dementia. alpha-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 alpha-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 alpha-synuclein, and to investigate the mechanistic basis of neurodegeneration caused by alpha-synuclein dysfunction.
|Title:||Parkinson's disease induced pluripotent stem cells with triplication of the alpha-synuclein locus|
|Open access status:||An open access publication|
|Publisher version:||http://www.ncbi.nlm.nih.gov/pmc/ articles/PMC3265381/?tool=pubmed|
|Keywords:||GENE DUPLICATION, DEMENTIA, ASSOCIATION, PATIENT, MODELS, BETA, SET, NEURODEGENERATION, PATHOGENESIS, FIBROBLASTS|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Neurology > Clinical Neuroscience|
UCL > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Neurology > Molecular Neuroscience
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