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

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

Authors :
Hsieh CH
Li L
Vanhauwaert R
Nguyen KT
Davis MD
Bu G
Wszolek ZK
Wang X
Source :
Cell metabolism [Cell Metab] 2019 Dec 03; Vol. 30 (6), pp. 1131-1140.e7. Date of Electronic Publication: 2019 Sep 26.
Publication Year :
2019

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.<br /> (Copyright © 2019 Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
1932-7420
Volume :
30
Issue :
6
Database :
MEDLINE
Journal :
Cell metabolism
Publication Type :
Academic Journal
Accession number :
31564441
Full Text :
https://doi.org/10.1016/j.cmet.2019.08.023