# Alpha-Synuclein Assemblies and Metal-Mediated Redox Mechanisms

> **NIH NIH R01** · VIRGINIA COMMONWEALTH UNIVERSITY · 2020 · $330,484

## Abstract

PROJECT SUMMARY
Elucidation of the etiopathology of protein-metal interactions has been in the spotlight of neurodegenerative
disease research for many years. The hallmark protein α-synuclein (αS), which is associated with the most
prevalent movement disorder - Parkinson’s disease (PD), remains unclear in regards to both function and
conformation. Similarly, questions pertaining to the role of transition biometals, namely copper and iron, are still
a mystery. This research aims to elucidate the effect of these biometals on different conformational states of αS,
contributing clarity to current controversies surrounding the native structure. In recent years, equally convincing
biochemical studies on erythrocyte- and brain-derived αS protein have been reported that argue in support of
two different native conformations for αS. The conventional conformation of αS has been described as an
intrinsically disordered monomer that can self-associate to form toxic oligomers as well as disease-relevant
insoluble aggregates termed Lewy bodies. Recent findings have supported a native tetrameric α-helical αS
conformation that is stabilized by hydrophobic interactions and that is resistant to aggregation, yet systematic
studies are sparse. Comprehensive studies on the role of copper and iron in these native conformations in
regards to structural influences, membrane affinity, protein-protein interactions, and/or ability to produce
functional/dysfunctional post-translational modifications have yet to be reported. The cross-disciplinary
approach described through this research strategy will aid in closing this gap within the biomedical community.
Likewise, an advancement in the understanding of tau/αS interactions as well as oxidative and/or nitrosative
molecular mechanisms will contribute to the elucidation of pathologically relevant disease pathways associated
with PD and may inspire new targets for drug development and/or clinical biomarkers.

## Key facts

- **NIH application ID:** 10022129
- **Project number:** 5R01GM134015-02
- **Recipient organization:** VIRGINIA COMMONWEALTH UNIVERSITY
- **Principal Investigator:** Heather R Lucas
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $330,484
- **Award type:** 5
- **Project period:** 2019-09-23 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10022129

## Citation

> US National Institutes of Health, RePORTER application 10022129, Alpha-Synuclein Assemblies and Metal-Mediated Redox Mechanisms (5R01GM134015-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10022129. Licensed CC0.

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