Parkin and PINK1 patient iPSC-derived midbrain dopamine neurons exhibit mitochondrial dysfunction and α-synuclein accumulation Journal Article
| Authors: | Chung, S. Y.; Kishinevsky, S.; Mazzulli, J. R.; Graziotto, J.; Mrejeru, A.; Mosharov, E. V.; Puspita, L.; Valiulahi, P.; Sulzer, D.; Milner, T. A.; Taldone, T.; Krainc, D.; Studer, L.; Shim, J. W. |
| Article Title: | Parkin and PINK1 patient iPSC-derived midbrain dopamine neurons exhibit mitochondrial dysfunction and α-synuclein accumulation |
| 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. © 2016 The Authors |
| Journal Title: | Stem Cell Reports |
| Volume: | 7 |
| Issue: | 4 |
| ISSN: | 2213-6711 |
| Publisher: | Cell Press |
| Date Published: | 2016-10-11 |
| Start Page: | 664 |
| End Page: | 677 |
| Language: | English |
| DOI: | 10.1016/j.stemcr.2016.08.012 |
| PROVIDER: | scopus |
| PMCID: | PMC5063469 |
| PUBMED: | 27641647 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 2 November 2016 -- Source: Scopus |
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