Investigators from The Parkinson’s Institute in Sunnyvale, CA, evaluated skin fibroblasts from a patient with parkinsonism carrying a triplication in the α-syn gene (SNCA). The cells showed a significant decrease in cell growth compared with healthy controls. “Our results in patient-derived fibroblasts were remarkably similar to overexpression experiments in cell lines and animal models. We detected a decrease in ATP production, a reduction in mitochondrial membrane potential, and a reduction in complex I activity,” commented Birgitt Schüle, MD, Assistant Professor, The Parkinson’s Institute. Furthermore, these fibroblasts proved to be more sensitive to the effects of the neurotoxin and herbicide paraquat compared to controls.
Mitochondrial function and cellular damage were partially rescued after siRNA knockdown of α-synuclein in fibroblasts after paraquat treatment. “We observed a significant increase in membrane potential and cellular ATP synthesis as well as a decrease in LDH release, supporting the hypothesis that α-synuclein expression levels are directly related to mitochondrial dysfunction,” said Dr. Schüle.
According to Dr. William Langston, the Scientific Director and CEO of The Parkinson’s Institute, and a co-author on the paper, these results are particularly exciting because they directly link a-syn over-expression and mitochondrial dysfunction in tissue from a parkinsonian patient. “One of the keys to unraveling this incurable and progressive disease is to solve the relationship between a-syn and mitochondrial dysfunction. In these results, we may have the first such link in human tissue,” Langston said.
The article is “Mitochondrial Dysfunction in Skin Fibroblasts from a Parkinson’s Disease Patient with an alpha-Synuclein Triplication” by Sally K. Mak, Deepika Tewari, James W. Tetrud, William J. Langston, and Birgitt Schüle. Journal of Parkinson’s Disease. 1(2). DOI 10.3233/JPD-2011-11205. Published by IOS Press.
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Birgitt Schüle, MD, is Assistant Professor, Clinical Molecular Geneticist at The Parkinson’s Institute, Sunnyvale, CA. Her team is developing a new model of “Parkinson’s disease in a petri-dish” and has created patient-derived stem cell lines and differentiated them into dopamine neurons. The goal is to utilize this new model to exploit disease mechanisms of PD, discover environmental toxins, and for innovative drug screening. Sponsors of this research are the California Institute for Regenerative Medicine (CIRM), Parkinson Alliance, and Brin Wojcicki Foundation
ABOUT THE PARKINSON’S INSTITUTE
The Parkinson’s Institute is America’s only independent non-profit organization combining clinical research, basic research and patient care, all under one roof. The Institute has gained a national and international recognition for its work by focusing on three aspects of Parkinson’s disease – determining its cause, providing excellence in patient care and focusing on research to find a cure. Founded in 1988, the Institute is committed to changing the landscape of PD treatment and research by closing the gap between discoveries in the laboratory and day to day patient care. Serving over 3000 patients, the Institute is also a leader in helping persons with Parkinson’s disease better manage their care and in carrying out clinical trials to develop new and better treatments for the disease. Learn more at www.thepi.org.
ABOUT THE JOURNAL OF PARKINSON’S DISEASE (JPD)
Launched in June 2011 the Journal of Parkinson’s Disease is dedicated to providing an open forum for original research in basic science, translational research and clinical medicine that will expedite our fundamental understanding and improve treatment of Parkinson’s disease. The journal is international and multidisciplinary and aims to promote progress in the epidemiology, etiology, genetics, molecular correlates, pathogenesis, pharmacology, psychology, diagnosis and treatment of Parkinson’s disease. It publishes research reports, reviews, short communications, and letters-to-the-editor and offers very rapid publication and an affordable open access option. www.journalofparkinsonsdisease.com
ABOUT IOS PRESS
Commencing its publishing activities in 1987, IOS Press (www.iospress.nl) serves the information needs of scientific and medical communities worldwide. IOS Press now (co-)publishes over 100 international journals and about 130 book titles each year on subjects ranging from computer sciences and mathematics to medicine and the natural sciences.
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