# Role of Parkin in Familial and Idiopathic Parkinson's Disease

> **NIH NIH R01** · UNIVERSITY OF FLORIDA · 2020 · $333,594

## Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by both motor and non-
motor disturbances. While the etiology of the disease is unknown, genetic mutations responsible
for familial forms of PD likely provide critical molecular insights into the underlying mechanisms of idiopathic
disease. Loss-of-function mutations in the ubiquitin E3 ligase parkin are the most common cause of autosomal
recessive PD. Parkin is now widely recognized as a pro-survival protein that possesses broad ranging effects
on mitochondrial biology, and beyond. A more complete comprehension of these functions will will lead to a
firmer understanding of the neurodegenerative process in PD, as well as the identification of new pathways
that may be targeted for disease modification. The long-term goal of our work is to uncover the molecular
machinery responsible for parkin's protective effects in neurons. We propose that both the cytosolic and
mitochondrial-localized pools of parkin play important roles in the maintenance of healthy neurons. This
application will explore the role of cytosolic parkin in its neuro-protective function in human neurons. Using
engineered isogenic and patient based WT and parkin null pluripotent stem cells differentiated to human
neuronal fates, we will uncover the conditions that activate the cytoplasmic pool of parkin. We will identify the
upstream proteins that control parkin activation and its protection against cell death in human neurons. Then,
we will explore the role of BH3 domains in the recognition of an expanding class of putative substrates of
cytoplasmic parkin E3 ligase activity. The pathways found to regulate neuronal parkin function may shed light
on innovative targets for therapeutic intervention to up-regulate parkin activity and induce neuro-protection in
neurologic disease.

## Key facts

- **NIH application ID:** 10197226
- **Project number:** 5R01NS065013-11
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Matthew J Lavoie
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $333,594
- **Award type:** 5
- **Project period:** 2010-08-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10197226

## Citation

> US National Institutes of Health, RePORTER application 10197226, Role of Parkin in Familial and Idiopathic Parkinson's Disease (5R01NS065013-11). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10197226. Licensed CC0.

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