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Parkinson's disease induced pluripotent stem cells with triplication of the α-synuclein locus

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 penetran...

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Detalles Bibliográficos
Autores principales: Devine, Michael J., Ryten, Mina, Vodicka, Petr, Thomson, Alison J., Burdon, Tom, Houlden, Henry, Cavaleri, Fatima, Nagano, Masumi, Drummond, Nicola J., Taanman, Jan-Willem, Schapira, Anthony H., Gwinn, Katrina, Hardy, John, Lewis, Patrick A., Kunath, Tilo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Pub. Group 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3265381/
https://www.ncbi.nlm.nih.gov/pubmed/21863007
http://dx.doi.org/10.1038/ncomms1453
Descripción
Sumario: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.