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

Michael J Devine, Mina Ryten, Petr Vodicka, Alison J Thomson, Tom Burdon, Henry Houlden, Fatima Cavaleri, Masumi Nagano, Nicola J Drummond, Jan-Willem Taanman, Anthony H Schapira, Katrina Gwinn, John Hardy, Patrick A Lewis, Tilo Kunath

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.
Original languageEnglish
Article number440
Number of pages10
JournalNature Communications
Issue numbern/a
Publication statusPublished - Aug 2011

Keywords / Materials (for Non-textual outputs)

  • Cell Differentiation
  • Cells, Cultured
  • Gene Dosage
  • Humans
  • Induced Pluripotent Stem Cells
  • Neurons
  • Parkinson Disease
  • alpha-Synuclein


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