# Investigating the role of C9orf72 in autophagic and metabolic dysregulation in ALS/FTD

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2022 · $567,481

## Abstract

Neurodegeneration is an increasing public health issue and remains an unsolved
biomedical challenge. Genetic discoveries have provided news avenues for investigating the
molecular mechanisms of several neurodegenerative diseases. Recently, a hexanucleotide
repeat expansion in a noncoding region of the C9orf72 gene was linked to the
neurodegenerative disease amyotrophic lateral sclerosis (ALS) and frontotemporal dementia
(FTD). ALS is characterized by loss of motor neurons, and the C9orf72 mutation represents the
most common genetic cause of both familial and sporadic ALS. FTD is characterized by
degeneration of the frontal and temporal lobes of the brain and is the second most common
type of dementia for people older than 65; the C9orf72 mutation is also the most common
genetic causes for FTD. The C9orf72 mutation is also found to contribute to Alzheimer’s disease
and Huntington’s disease. Despite intense efforts and rapid advances, our understanding of the
disease mechanisms and treatment strategies for C9orf72-linked ALS/FTD are still at the early
stages. To help relieve the public health burden associated with these diseases, it is important
to understand the mechanisms underlying the pathogenesis. We have recently discovered that
C9orf72 plays an important role in the regulation of autophagy and related metabolic processes,
suggesting that further studies of C9orf72 functions could shed light on the mechanism of
ALS/FTD pathogenesis. The goal of the proposed project is to elucidate the mechanisms
through which dysregulation of C9orf72 functions leads to molecular defects and neuronal
toxicity. The specific aims are to identify the central mechanisms through which C9orf72
regulates autophagy and related metabolism, to delineate the pathways through which the
pathogenesis is generated, and to identify potential intervention strategies. The proposed
studies, which combine biochemical, molecular, and genetic approaches, are expected to
provide insight into fundamental mechanisms of neurodegeneration in ALS/FTD that may
ultimately leads to novel approaches for treating these devastating neurodegenerative diseases.

## Key facts

- **NIH application ID:** 10400837
- **Project number:** 5R01NS089616-08
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Jiou Wang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $567,481
- **Award type:** 5
- **Project period:** 2015-05-15 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10400837

## Citation

> US National Institutes of Health, RePORTER application 10400837, Investigating the role of C9orf72 in autophagic and metabolic dysregulation in ALS/FTD (5R01NS089616-08). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10400837. Licensed CC0.

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