# Novel chaperones and neurodegeneration

> **NIH NIH R01** · DUKE UNIVERSITY · 2022 · $50,559

## Abstract

Abstract
Protein quality control is essential to prevent the accumulation of proteotoxic species that cause
neurodegenerative diseases. Therefore, understanding how cells respond to proteotoxic species is essential for
developing therapies to treat these diseases. One class of proteins that are especially prone to aggregation are
proteins with homopolymeric amino acid repeats, including polyglutamine repeats. Expanded polyglutamine
repeats cause a class of nine neurodegenerative diseases and understanding how cells deal with long
polyglutamine repeats will inform us about ways to treat the polyglutamine diseases and many other
neurodegenerative diseases. My group has taken a unique approach to investigating how cells deal with long
polyglutamine repeats. Instead of modeling polyglutamine repeats in organisms that have protein aggregation,
we have identified the cellular slime mold Dictyostelium discoideum as being naturally resistant to polyglutamine
aggregation. Dictyostelium is likely able to accomplish this due to the fact that this organism naturally encodes
nearly 2,500 polyglutamine repeats with many surpassing the disease threshold in humans. Together this raises
the question: What novel mechanisms do Dictyostelium utilize to suppress protein aggregation? Here we
propose to begin to use a comparative biology-based approach to identify how Dictyostelium respond to cellular
stressors that drive protein aggregation and neuronal death. These findings can then be utilized in human cells
to determine if similar strategies can be used to enhance proteostasis and treat neurodegenerative diseases.

## Key facts

- **NIH application ID:** 10620386
- **Project number:** 3R01NS112191-04S2
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Kenneth Matthew Scaglione
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $50,559
- **Award type:** 3
- **Project period:** 2022-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10620386

## Citation

> US National Institutes of Health, RePORTER application 10620386, Novel chaperones and neurodegeneration (3R01NS112191-04S2). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10620386. Licensed CC0.

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