Journal
CELL METABOLISM
Volume 30, Issue 6, Pages 1131-+Publisher
CELL PRESS
DOI: 10.1016/j.cmet.2019.08.023
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Funding
- Klingenstein Fund
- CIRM
- NINDS [RO1NS089583]
- Archer Fund
- Stanford Parkinson's Disease Seed Grant
- Stanford SPARK
- Belgian American Education Foundation
- Sol Goldman Charitable Trust
- Donald G. and Jodi P. Heeringa Family
- Haworth Family Professorship in Neurodegenerative Diseases Fund
- Albertson Parkinson's Research Foundation
- Mayo Clinic Center for Regenerative Medicine
- MJFF
- AbbVie
- Avid
- Biogen
- Bristol-Myers Squibb
- COVANCE
- GE Healthcare
- Genentech
- GlaxoSmithKline
- Lilly
- Lundbeck
- Merck
- Meso Scale Discovery
- Pfizer
- Piramal
- Roche
- Servier
- UCB
- Stanford ADRC Neuropathology and Biospecimens Core [P50 AG047366]
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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.
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