# Modulating selective autophagy to modify Huntington's disease

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2022 · $415,372

## Abstract

PROJECT SUMMARY
Although a common theme across adult onset neurodegenerative diseases, the pathogenic role of aggregated
proteins is a continuous topic of debate. For the incurable familial neurodegenerative disorder Huntington's
disease (HD), resolving the accumulation of mutant huntingtin (Htt) (neuronal or cytoplasmic) is highly correlated
with favorable therapeutic outcomes. Whether targeting aggregate clearance per se is beneficial, however, has
remained unclear. We have previously identified a pathway by which aggregated proteins are selectively
eliminated by the lysosome-mediated pathway macroautophagy. We found that the protein Alfy is central for the
selective turnover of aggregates in cell based systems. During the previous funding period, we used a mouse
genetics and cell biology to determine that Alfy is indeed essential turnover of aggregated proteins in adult brain,
and diminishing Alfy levels in vivo modifies disease onset. In this renewal application, we will use genetic and
molecular based approaches to determine if augmenting Alfy levels promotes the elimination of aggregated
nuclear and cytoplasmic proteins, the mechanism by which a genetic variant of Alfy might delay the age of onset
of MD, and the molecular mechanism by which Alfy permits aggregate clearance.
.

## Key facts

- **NIH application ID:** 10382236
- **Project number:** 5R01NS077111-08
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Ai Yamamoto
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $415,372
- **Award type:** 5
- **Project period:** 2012-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10382236

## Citation

> US National Institutes of Health, RePORTER application 10382236, Modulating selective autophagy to modify Huntington's disease (5R01NS077111-08). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10382236. Licensed CC0.

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