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.