# Genome Wide Analysis of Alpha-Synuclein Neurotoxicity

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2020 · $585,729

## Abstract

Parkinson's disease is the most common neurodegenerative movement disorder and is characterized
pathologically by the intraneuronal deposition of abnormally phosphorylated and aggregated α-synuclein
protein. Abnormal deposition of α-synuclein into neuronal and glial aggregates is also the primary pathologic
feature of a group of collectively even more common disorders, termed the α-synucleinopathies. To define
the molecular mechanisms controlling α-synuclein induced neurodegeneration we and others have modeled
α-synucleinopathies in the simple and powerful genetic model organism Drosophila. Genetic, biochemical
and cell biological experiments in Drosophila have provided important clues regarding the pathogenesis of
α-synucleinopathies. However, the unbiased forward genetic screens providing the bases for these studies,
while valuable, have to date remained incomplete. Here we propose to use a newly created and powerful
Drosophila model of α-synucleinopathies to perform a comprehensive genetic analysis of α-synuclein
neurotoxicity in vivo. These studies will for the first time provide a broad analysis of mechanisms controlling
α-synuclein toxicity to postmitotic neurons and should identify many new high-value therapeutic targets.
Our studies will be particularly important as more and more data emerges from genome wide associated
studies showing genetic influences on Parkinson's disease and related α-synucleinopathies, but with little
clear evidence as to the mechanism of action of these newly identified gene products in neurodegenerative
disease pathogenesis.

## Key facts

- **NIH application ID:** 9995036
- **Project number:** 5R01NS098821-04
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** MEL B FEANY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $585,729
- **Award type:** 5
- **Project period:** 2017-09-25 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9995036

## Citation

> US National Institutes of Health, RePORTER application 9995036, Genome Wide Analysis of Alpha-Synuclein Neurotoxicity (5R01NS098821-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9995036. Licensed CC0.

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