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.

http://www.journalofparkinsonsdiseas...ysfunction.pdf