Journal
SCIENCE TRANSLATIONAL MEDICINE
Volume 4, Issue 141, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scitranslmed.3003985
Keywords
-
Categories
Funding
- American Recovery and Reinvestment Act-NIH/National Institute of Neurological Disorders and Stroke (NINDS) [1RC2NS070276]
- NIH [1U24NS078338-01]
- Michael J. Fox Foundation
- Harvard Stem Cell Institute
- Miller Consortium for the Development of Nervous System Therapies
- Orchard Foundation
- Harold and Ronna Cooper family
- Consolidated Anti-Aging Foundation
- Poul Hansen family
- NIH/NINDS [NS057567, P50NS072187, NS38377]
- Mayo Clinic Florida (MCF) Research Committee CR [90052030]
- Dystonia Medical Research Foundation
- Maryland Stem Cell Research Foundation [2007-MSCRFI-0420-00]
- Hermann and Lilly Schilling Foundation
- National Research Foundation of Korea [2012R1A1B5003338, 2011-0030775] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available