Parkin and PINK1 Patient iPSC-Derived Midbrain Dopamine Neurons Exhibit Mitochondrial Dysfunction and alpha-Synuclein Accumulation
- Authors
- Chung, Sun Young; Kishinevsky, Sarah; Mazzulli, Joseph R.; Graziotto, John; Mrejeru, Ana; Mosharov, Eugene V.; Puspita, Lesly; Valiulahi, Parvin; Sulzer, David; Milner, Teresa A.; Taldone, Tony; Krainc, Dimitri; Studer, Lorenz; Shim, Jae-Won
- Issue Date
- 11-Oct-2016
- Publisher
- Cell Press
- Keywords
- Parkinson's disease
- Citation
- Stem Cell Reports, v.7, no.4, pp 664 - 677
- Pages
- 14
- Journal Title
- Stem Cell Reports
- Volume
- 7
- Number
- 4
- Start Page
- 664
- End Page
- 677
- URI
- https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/8680
- DOI
- 10.1016/j.stemcr.2016.08.012
- ISSN
- 2213-6711
- Abstract
- Parkinson's disease (PD) is characterized by the selective loss of dopamine neurons in the substantia nigra; however, the mechanism of neurodegeneration in PD remains unclear. A subset of familial PD is linked to mutations in PARK2 and PINK1, which lead to dysfunctional mitochondria-related proteins Parkin and PINK1, suggesting that pathways implicated in these monogenic forms could play a more general role in PD. We demonstrate that the identification of disease-related phenotypes in PD-patient-specific induced pluripotent stem cell (iPSC)-derived midbrain dopamine (mDA) neurons depends on the type of differentiation protocol utilized. In a floor-plate-based but not a neural-rosette-based directed differentiation strategy, iPSC-derived mDA neurons recapitulate PD phenotypes, including pathogenic protein accumulation, cell-type-specific vulnerability, mitochondrial dysfunction, and abnormal neurotransmitter homeostasis. We propose that these form a pathogenic loop that contributes to disease. Our study illustrates the promise of iPSC technology for examining PD pathogenesis and identifying therapeutic targets.
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Collections - Graduate School > Department of Integrated Biomedical Science > 1. Journal Articles
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