# Investigation of Superoxide Dismutase I in Parkinson's Disease

> **NIH NIH P20** · MC LAUGHLIN RESEARCH INSTITUTE · 2024 · $360,000

## Abstract

Project III: SUMMARY
Increasing evidence indicates that neurodegenerative diseases may share overlapping proteinopathies and
common molecular mechanisms. The overall goal of this project is to enhance our understanding of the role of
two proteins in Parkinson’s Disease (PD). PD is the second most common neurodegenerative disease in the
United States and is characterized by the loss of dopaminergic neurons of the substantia nigra. Although most
PD cases are idiopathic, genetic causes have been identified including mutations and copy number variants of
the gene that encodes alpha synuclein (SNCA) protein, a major component of Lewy body aggregates observed
in postmortem PD brain tissue. SNCA has been shown to possess prion properties in that it can induce misfolding
and aggregation that can spread from cell to cell. Much less is known about other proteins that may modulate
SNCA aggregation and have an impact on PD pathology. This project addresses the hypothesis that Superoxide
Dismutase 1 (SOD1) aggregates are correlated with SNCA aggregates in idiopathic PD brain and that they
exacerbate disease progression in concert with misfolded SNCA. SOD1 is a major cytoplasmic antioxidant
enzyme that metabolizes superoxide radicals; mutations in the SOD1 gene were the first mutations linked to the
neurodegenerative disorder Amyotrophic Lateral Sclerosis (ALS). Although several reports indicate SOD1
aggregates occur in postmortem PD brain tissue, the role of SOD1 in PD is not clear. This project builds on
substantial preliminary data that demonstrates development of a SOD1 aggregation assay that can detect and
propagate misfolded SOD1 in postmortem human neural tissues with high specificity and sensitivity. To address
the hypothesis, two aims are proposed: Specific Aim 1 is focused on the use of human tissues and cells to
examine the propagation and toxicity of SOD1 aggregates, whereas Specific Aim 2 uses mouse models to test
the hypothesis. We will quantify SNCA and SOD1 aggregates in postmortem idiopathic PD brain regions,
examine neurotoxicity from idiopathic PD-SOD1 on dopaminergic neurons, and determine whether the presence
of the human SOD1 wild type allele exacerbates neurobehavioral deficits and protein aggregation in a PD mouse
model expressing human SNCA. This project is significant as it addresses the underlying molecular pathology
of a common neurodegenerative disease; the project is also significant in that PD has an outsized impact in rural
communities, where incidence of PD has been reported to be higher and access to specialists is limited relative
to urban areas. Several aspects of the project are innovative including: 1) the hypothesis, based on shared
proteinopathy of SNCA and SOD1, 2) the use of novel tools such as the first SOD1 real time quaking induced
conversion (RT-QuIC) assay, and 3) the use of complementary but independent studies in humans and mouse
models. Outcomes of this study will shed light on the role of SOD1 in idiopathic PD...

## Key facts

- **NIH application ID:** 10771507
- **Project number:** 1P20GM152335-01
- **Recipient organization:** MC LAUGHLIN RESEARCH INSTITUTE
- **Principal Investigator:** Moses Leavens
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $360,000
- **Award type:** 1
- **Project period:** 2024-01-01 → 2028-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10771507

## Citation

> US National Institutes of Health, RePORTER application 10771507, Investigation of Superoxide Dismutase I in Parkinson's Disease (1P20GM152335-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10771507. Licensed CC0.

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