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Miro1 Marks Parkinson's Disease Subset and Miro1 Reducer Rescues Neuron Loss in Parkinson's Models

Cell Metab.. 2019; 
Hsieh CH1, Li L1, Vanhauwaert R1, Nguyen KT2, Davis MD3, Bu G3, Wszolek ZK4, Wang X5.
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摘要

The identification of molecular targets and pharmacodynamic markers for Parkinson's disease (PD) will empower more effective clinical management and experimental therapies. Miro1 is localized on the mitochondrial surface and mediates mitochondrial motility. Miro1 is removed from depolarized mitochondria to facilitate their clearance via mitophagy. Here, we explore the clinical utility of Miro1 for detecting PD and for gauging potential treatments. We measure the Miro1 response to mitochondrial depolarization using biochemical assays in skin fibroblasts from a broad spectrum of PD patients and discover that more than 94% of the patients' fibroblast cell lines fail to remove Miro1 following depolarization. We ide... More

关键词

Miro1; Parkinson; biomarker; diet; fibroblast; fly; iPSC; mitochondria; mitophagy; neurons; small molecules; therapy