Metformin rescues Parkinson’s disease phenotypes caused by hyperactive mitochondria

著者: Danielle E. Mor, Salman Sohrabi, Rachel Kaletsky, William Keyes, Alp Tartici, Vrinda Kalia, Gary W. Miller, Coleen T. Murphy - Proceedings of the National Academy of Sciences, PNAS 2020 被引用: 159

Significance Uncovering the role of defective metabolism in Parkinson’s disease (PD) may lead to the discovery of disease-modifying therapies. We recently linked branched-chain amino acid (BCAA) metabolism with PD, yet the underlying mechanisms were unknown. We now report the unexpected finding that BCAA metabolic dysfunction causes Parkinson’s-like motor deficits and neurodegeneration by inducing a state of hyperactive mitochondria. We found that the type 2 diabetes medication metformin is able to rescue neuronal viability by reducing mitochondrial respiration. These results offer mitochondrial hyperactivity as a new potential mechanism of mitochondrial dysfunction in Parkinson’s disease, and suggest that efforts to reduce mitochondrial respiration early in the disease—potentially by metformin treatment—may be efficacious.