RT Journal Article SR Electronic T1 Pharmacological Rescue of Mitochondrial Deficits in iPSC-Derived Neural Cells from Patients with Familial Parkinson’s Disease JF Science Translational Medicine FD American Association for the Advancement of Science SP 141ra90 OP 141ra90 DO 10.1126/scitranslmed.3003985 VO 4 IS 141 A1 Cooper, Oliver A1 Seo, Hyemyung A1 Andrabi, Shaida A1 Guardia-Laguarta, Cristina A1 Graziotto, John A1 Sundberg, Maria A1 McLean, Jesse R. A1 Carrillo-Reid, Luis A1 Xie, Zhong A1 Osborn, Teresia A1 Hargus, Gunnar A1 Deleidi, Michela A1 Lawson, Tristan A1 Bogetofte, Helle A1 Perez-Torres, Eduardo A1 Clark, Lorraine A1 Moskowitz, Carol A1 Mazzulli, Joseph A1 Chen, Li A1 Volpicelli-Daley, Laura A1 Romero, Norma A1 Jiang, Houbo A1 Uitti, Ryan J. A1 Huang, Zhigao A1 Opala, Grzegorz A1 Scarffe, Leslie A. A1 Dawson, Valina L. A1 Klein, Christine A1 Feng, Jian A1 Ross, Owen A. A1 Trojanowski, John Q. A1 Lee, Virginia M.-Y. A1 Marder, Karen A1 Surmeier, D. James A1 Wszolek, Zbigniew K. A1 Przedborski, Serge A1 Krainc, Dimitri A1 Dawson, Ted M. A1 Isacson, Ole YR 2012 UL http://stm.sciencemag.org/content/4/141/141ra90.abstract AB 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 Q10, 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.