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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.
- 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.)
- Subjects :
- Adult
Aged
Animals
Antiparkinson Agents therapeutic use
Biomarkers metabolism
Drosophila
Female
Fibroblasts
HEK293 Cells
Humans
Induced Pluripotent Stem Cells
Male
Middle Aged
Neurons pathology
Antiparkinson Agents pharmacology
Drosophila Proteins antagonists & inhibitors
Drosophila Proteins metabolism
Mitochondrial Proteins antagonists & inhibitors
Mitochondrial Proteins metabolism
Nerve Degeneration drug therapy
Neurons drug effects
Parkinson Disease drug therapy
Parkinson Disease metabolism
Parkinson Disease pathology
rho GTP-Binding Proteins antagonists & inhibitors
rho GTP-Binding Proteins metabolism
Subjects
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