# Mechanistic insight into RNA-mediated toxicity of C9orf72-linked ALS/FTD

> **NIH NIH R21** · EMORY UNIVERSITY · 2020 · $191,279

## Abstract

Expanded GGGGCC (G4C2) hexanucleotide repeats in the C9orf72 gene were recently identified as the
most common genetic cause of Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD), two
neurodegenerative disorders with genetic and pathological overlap. Repeat-RNA-toxicity mediated by
sequestering key RNA binding proteins is thought to play key roles in c9ALS/FTD pathogenesis. However,
which RNA binding protein(s) might be sequestered by long G4C2 repeat RNAs is still unknown. We propose to
identify RNA-protein interactions in c9ALS/FTD using disease-relevant repeat lengths and cell models, and by
comparison to interacting-proteins of (TG3C2) repeats, a similar repeat expansion that leads to a clinically
disparate disease Spinocerebellar Ataxia type 36 (SCA36). The identified RNA binding protein(s) by the G4C2
repeats will be further validated in c9ALS/FTD patient postmortem brain samples and its functions will be
studied in iPS-derived motor neurons and in mice. Results from this proposal will provide new insight into the
cellular cascades that cause neurodegeneration in c9ALS/FTD.

## Key facts

- **NIH application ID:** 10019613
- **Project number:** 5R21NS114908-02
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** GARY J BASSELL
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $191,279
- **Award type:** 5
- **Project period:** 2019-09-18 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10019613

## Citation

> US National Institutes of Health, RePORTER application 10019613, Mechanistic insight into RNA-mediated toxicity of C9orf72-linked ALS/FTD (5R21NS114908-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10019613. Licensed CC0.

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