4.5 Article

Miro1 Impairment in a Parkinson's At-Risk Cohort

Journal

FRONTIERS IN MOLECULAR NEUROSCIENCE
Volume 14, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fnmol.2021.734273

Keywords

Parkinson's disease; IPSC; mitophagy; risk; Miro1

Categories

Funding

  1. Michael J. Fox Foundation (MJFF) [18195]
  2. MJFF
  3. Abbvie
  4. Avid
  5. Biogen
  6. Bristol-Myers Squibb
  7. COVANCE
  8. GE Healthcare
  9. Genentech
  10. GlaxoSmithKline
  11. Lilly
  12. Lundbeck
  13. Merck
  14. Meso Scale Discovery
  15. Pfizer
  16. Piramal
  17. Roche
  18. Servier
  19. UCB
  20. Stanford WHSDM Center

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The study identified the mitochondrial protein Miro1 as potentially a molecular marker for Parkinson's disease and at-risk individuals. The response of Miro1 to mitochondrial depolarization was significantly associated with PD risk, suggesting its potential use for detecting both PD and at-risk populations. Tracking the Miro1 marker could assist in diagnosis and Miro1-based drug discoveries.
There is a lack of reliable molecular markers for Parkinson's disease (PD) patients and at-risk individuals. The detection of the pre-symptomatic population of PD will empower more effective clinical intervention to delay or prevent disease onset. We have previously found that the mitochondrial protein Miro1 is resistant to mitochondrial depolarization-induced degradation in fibroblasts from a large number of PD patients and several at-risk individuals. Therefore, Miro1 has the potential to molecularly label PD populations. In order to determine whether Miro1 could serve as a molecular marker for the risk of PD, here we examine the Miro1 response to mitochondrial depolarization by biochemical approaches in induced pluripotent stem cells from a cohort of at-risk individuals. Our results show that the Miro1 phenotype is significantly associated with PD risk. We propose that Miro1 is a promising molecular marker for detecting both PD and at-risk populations. Tracking this Miro1 marker could aid in diagnosis and Miro1-based drug discoveries.

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