# Novel chaperones and neurodegeneration

> **NIH NIH R01** · DUKE UNIVERSITY · 2022 · $26,037

## Abstract

Abstract
The polyglutamine diseases are a class of nine neurodegenerative diseases caused by the expansion of a CAG
trinucleotide repeat in the coding region of specific genes. Translation of these expanded CAG repeats results
in the production of a protein with an expanded polyglutamine tract. Proteins with these expanded polyglutamine
tracts aggregate and result in neuronal toxicity. Therefore, the identification of factors that suppress
polyglutamine aggregation may lead to the development of therapies for the polyglutamine diseases. In most
model organisms expression of a polyglutamine repeat results in aggregation, however, we have found that the
social amoeba Dictyostelium discoideum naturally expresses thousands of polyglutamine repeats that remain
soluble. Furthermore, we and others have found that expression of a polyglutamine expanded huntingtin exon 1
construct (mHtt) that aggregates in other model organisms remains soluble in Dictyostelium. This has led us to
hypothesize that Dictyostelium encodes for novel proteins and/or pathways that suppresses polyglutamine
aggregation. To identify factors that suppress polyglutamine aggregation we have carried out a screen and
identified a single gene that suppresses polyglutamine aggregation in Dictyostelium. One caveat to this screen
was that it was labor intensive and only covered less than five percent of the genome. To overcome this limitation
Ms. Felicia Williams has established a new screening protocol that will allow near genome-wide saturation. She
will learn new methodology, gain technical expertise, publish high impact research, and prepare herself to obtain
a postdoctoral fellowship. Overall this project will complement the parental grant and ongoing experiments in the
lab to identify novel mechanisms to suppress polyglutamine aggregation and determine if these mechanisms
can be translated into therapies.

## Key facts

- **NIH application ID:** 10525677
- **Project number:** 3R01NS112191-03S1
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Kenneth Matthew Scaglione
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $26,037
- **Award type:** 3
- **Project period:** 2019-07-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10525677

## Citation

> US National Institutes of Health, RePORTER application 10525677, Novel chaperones and neurodegeneration (3R01NS112191-03S1). Retrieved via AI Analytics 2026-06-08 from https://api.ai-analytics.org/grant/nih/10525677. Licensed CC0.

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