# Biophysical determination of the underlying cause of α-Syn oligomer toxicity

> **NIH NIH R35** · TEXAS A&M AGRILIFE RESEARCH · 2021 · $286,722

## Abstract

ABSTRACT
Parkinson disease (PD) is the second most common neurodegenerative disease that
affects nearly 5 millions of people around the world. PD is associated with intracellular
aggregation of α-synuclein (α-Syn), a small protein that is involved in the regulation of lipid
metabolism and synaptic vesicle trafficking. A growing body of evidence suggests that
alterations in lipid profile, which were observed in both brain and plasma, can be directly
linked to the onset of α-Syn aggregation. We hypothesize that the toxicity of α-Syn
aggregates is determined by their structure, which in turn is controlled by the lipid
composition of neuronal membranes. Our group pioneered development of a label-free,
non-invasive and non-destructive approach that can be used to determine the structural
organization of individual α-Syn aggregates. We will use this innovative biophysical
imaging approach to unravel protein secondary structure of α-Syn oligomers grown in the
presence of different lipids. We will investigate toxicity of these oligomers on primary
dopaminergic neurons from midbrain, striatal, and cortical areas of the mouse brains. This
will reveal the relationship between the structure of α-Syn oligomers and their toxicity. The
proposed work also aims to determine the extent to which α-Syn oligomers with different
structures exert toxic effects to the specific subsets of neurons.

## Key facts

- **NIH application ID:** 10275841
- **Project number:** 1R35GM142869-01
- **Recipient organization:** TEXAS A&M AGRILIFE RESEARCH
- **Principal Investigator:** Dmitry Kurouski
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $286,722
- **Award type:** 1
- **Project period:** 2021-08-15 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10275841

## Citation

> US National Institutes of Health, RePORTER application 10275841, Biophysical determination of the underlying cause of α-Syn oligomer toxicity (1R35GM142869-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10275841. Licensed CC0.

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