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

Abstract	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 identify a small molecule that can repair this defect of Miro1 in PD fibroblasts. Treating patient-derived neurons and fly models with this compound rescues the locomotor deficits and dopaminergic neurodegeneration. Our results indicate that tracking this Miro1 marker and engaging in Miro1-based therapies could open new avenues to personalized medicine.
Authors	Chung-Han Hsieh, Li Li, Roeland Vanhauwaert, Kong T Nguyen, Mary D Davis, Guojun Bu, Zbigniew K Wszolek, Xinnan Wang
Journal	Cell metabolism (Cell Metab) Vol. 30 Issue 6 Pg. 1131-1140.e7 (12 03 2019) ISSN: 1932-7420 [Electronic] United States
PMID	31564441 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Copyright	Copyright © 2019 Elsevier Inc. All rights reserved.
Chemical References	Antiparkinson Agents Biomarkers Drosophila Proteins Mitochondrial Proteins Miro protein, Drosophila RHOT1 protein, human rho GTP-Binding Proteins
Topics	Adult Aged Animals Antiparkinson Agents (pharmacology, therapeutic use) Biomarkers (metabolism) Drosophila Drosophila Proteins (antagonists & inhibitors, metabolism) Female Fibroblasts HEK293 Cells Humans Induced Pluripotent Stem Cells Male Middle Aged Mitochondrial Proteins (antagonists & inhibitors, metabolism) Nerve Degeneration (drug therapy) Neurons (drug effects, pathology) Parkinson Disease (drug therapy, metabolism, pathology) rho GTP-Binding Proteins (antagonists & inhibitors, metabolism)

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