Pharmacological rescue of mitochondrial deficits in iPSC-derived neural cells from patients with familial Parkinson's disease
- Title
- Pharmacological rescue of mitochondrial deficits in iPSC-derived neural cells from patients with familial Parkinson's disease
- Author
- 서혜명
- Keywords
- cytology; nerve cell; Humans; Protein-Serine-Threonine Kinases; PINK1 gene; Mitochondria; Ubiquinone; pluripotent stem cell; leucine rich repeat kinase 2; proton radiation; Indoles; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; female; gene; hum
- Issue Date
- 2012-07
- Publisher
- American Association for the Advancement of Science
- Citation
- Science Translational Medicine, v. 4, NO. 141, article no. 141ra90, Page. 1-14
- Abstract
- Parkinson's disease (PD) is a common neurodegenerative disorder caused by genetic and environmental factors that results in degeneration of the nigrostriatal dopaminergic pathway in the brain. We analyzed neural cells generated from induced pluripotent stem cells (iPSCs) derived from PD patients and presymptomatic individuals carrying mutations in the PINK1 (PTEN-induced putative kinase 1) and LRRK2 (leucine-rich repeat kinase 2) genes, and compared them to those of healthy control subjects. We measured several aspects of mitochondrial responses in the iPSC-derived neural cells including production of reactive oxygen species, mitochondrial respiration, proton leakage, and intraneuronal movement of mitochondria. Cellular vulnerability associated with mitochondrial dysfunction in iPSC-derived neural cells from familial PD patients and at-risk individuals could be rescued with coenzyme Q 10, rapamycin, or the LRRK2 kinase inhibitor GW5074. Analysis of mitochondrial responses in iPSC-derived neural cells from PD patients carrying different mutations provides insight into convergence of cellular disease mechanisms between different familial forms of PD and highlights the importance of oxidative stress and mitochondrial dysfunction in this neurodegenerative disease.
- URI
- https://www.science.org/doi/10.1126/scitranslmed.3003985https://repository.hanyang.ac.kr/handle/20.500.11754/184276
- ISSN
- 1946-6234;1946-6242
- DOI
- 10.1126/scitranslmed.3003985
- Appears in Collections:
- COLLEGE OF SCIENCE AND CONVERGENCE TECHNOLOGY[E](과학기술융합대학) > ETC
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