# Prion and non-prion induction mechanisms of alpha-synuclein pathology

> **NIH NIH R01** · UNIVERSITY OF FLORIDA · 2021 · $379,614

## Abstract

The presence of  a-synuclein brain aggregates are a hallmark of a
spectrum of neurodegenerative disorders, including Parkinson disease, Lewy body dementia
and multiple system atrophy, and are associated with disease severity. Several studies suggest
that this a-synuclein pathology may spread during disease progression by a self-templating
mechanism and that nervous tissue containing aggregated a-synuclein could be a risk for
disease transmission similar to prion disease. However, we recently demonstared that a non--
synuclein factor enriched in central nervous tissue-derived white matter is sufficient to induce
the progressive formation of a-synuclein inclusion pathology that can mimic prion-like
transmission of  a-synuclein pathology. These observations suggest the presence of a yet
unidentified factor that can trigger a-synucleinopathy, similar to protein X, a putative auxiliary
factor in prionopathies. Furthermore, this factor may have a pathogenic role in human disease.
To resolve critical issues at the core of whether synucleinopathies should be re-classified as
prion disorders and to elucidate mechanisms involved in disease progression we propose the
following aims: 1) characterize the biochemical properties of the non-a-synuclein component
that can trigger the progressive formation of a-synuclein, 2) determine whether a-synuclein
aggregates can truely exhibit properties expected of classical prions, and 3) determine the
relative prion-like transmission properties of central nervous tissue from patients with multiple
system atrophy and Lewy body dementia, two phenotypically distinctive a-synucleinopathies.
These highly integrated aims will provide important mechanistic and biologically relevant insights
into the mechanisms and risk of pathology transmission from tissues containing a-synucleinopathies.

## Key facts

- **NIH application ID:** 10214707
- **Project number:** 5R01NS100876-04
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** DAVID R BORCHELT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $379,614
- **Award type:** 5
- **Project period:** 2018-09-15 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10214707

## Citation

> US National Institutes of Health, RePORTER application 10214707, Prion and non-prion induction mechanisms of alpha-synuclein pathology (5R01NS100876-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10214707. Licensed CC0.

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