# Defining the Mechanism of Alpha-synuclein Dependent Restriction of Viral Neuroinvasion

> **NIH VA I01** · VA EASTERN COLORADO HEALTH CARE SYSTEM · 2020 · —

## Abstract

Alpha-synuclein (syn) is a neuron-specific protein known to cause Parkinson’s disease. The protein is always
expressed and recent work has shown that syn mis-folds into fibrils in peripheral neurons in the
gastrointestinal track and the olfactory bulb. These fibrils then spread to the central nervous system in select
individuals resulting in neurodegenerative diseases like Parkinson’s disease or Diffuse Lewy Body Dementia.
Veteran populations are at risk for developing neurodegenerative diseases as they age and work to
understand the cause of Parkinson’s disease will yield new approaches to treat and prevent neurodegenerative
diseases. We have discovered that virus infections initiate post-translational modifications of syn that are
associated with Parkinson’s disease. Moreover, our prior work has shown that syn functions to inhibit virus
infections from spreading from the peripheral nerves to the central nervous system.
Taken together, our findings reveal a stunning new understanding of the role of syn in the brain. We
hypothesize that viral infections induce post-translational modifications in syn as an antiviral mechanism.
While this response is acutely protective, exposure increases the risk of syn-induced pathology that can
result in long term neurodegenerative diseases found in Parkinson’s disease. We will evaluate our hypothesis
by defining the mechanism of syn-induced inhibition of WNV infection in neurons and defining the interactions
between syn post-translational modifications and α-syn fibril spread. We will utilize techniques in molecular
virology in combination with established mouse models in the field of Parkinson’s research to define the
specific interactions and consequences of the interactions between syn and viral infection in the brain. If the
proposed studies are completed as outlined, we will provide novel data that will have significant impact on the
field of Parkinson’s disease research and neurovirology. Thus, our proposed work will have significant benefits
for our veteran populations by improving health and providing potential new approaches to prevent and treat
neurodegenerative processes like Parkinson’s disease.

## Key facts

- **NIH application ID:** 9932283
- **Project number:** 5I01BX003863-04
- **Recipient organization:** VA EASTERN COLORADO HEALTH CARE SYSTEM
- **Principal Investigator:** John David Beckham
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2017-07-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9932283

## Citation

> US National Institutes of Health, RePORTER application 9932283, Defining the Mechanism of Alpha-synuclein Dependent Restriction of Viral Neuroinvasion (5I01BX003863-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9932283. Licensed CC0.

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