# Understanding the Cellular Basis of Movement Disorders

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2022 · $532,040

## Abstract

Project Summary
Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurodegenerative disease caused by a CAG
trinucleotide repeat expansion in ATXN1 that leads to an abnormally long polyglutamine tract in the
subsequent protein, ataxin-1 (ATXN1). Mutant ATXN1 has a propensity to misfold, resist cellular degradation,
and increase in toxicity as its levels rise. This toxicity occurs by a gain of function mechanism with evidence
point to transcriptional derangements as an early, presymptomatic pathogenic event. We recently discovered
that the earliest abnormalities in Purkinje cells (cells that are most vulnerable in SCA1) are not caused by cell-
autonomous changes but in a non-cell autonomous manner by affecting the proliferation and fate of cerebellar
post-natal stem cells. In this proposal, we will test the hypothesis that the underlying SCA1 pathology has its
roots in early developmental processes and that if these defects are overcome one might be able to delay or
ameliorate later neurodegeneration, thus paving the way for therapy for this currently untreatable condition.

## Key facts

- **NIH application ID:** 10403448
- **Project number:** 5R01NS082351-09
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Puneet Opal
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $532,040
- **Award type:** 5
- **Project period:** 2013-05-15 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10403448

## Citation

> US National Institutes of Health, RePORTER application 10403448, Understanding the Cellular Basis of Movement Disorders (5R01NS082351-09). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10403448. Licensed CC0.

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