# Developing an Anti-proteotoxicity Therapy for Neurodegenerative Diseases

> **NIH NIH R41** · REZIGENE, LLC · 2024 · $349,854

## Abstract

Project Summary
Protein quality control is a fundamental system in the cell that is important for normal cellular
functions and defense against potential pathogenic insults. Protein misfolding and aggregation
are a central feature of many neurodegenerative diseases including Alzheimer’s disease (AD),
frontotemporal dementia (FTD), and amyotrophic lateral sclerosis (ALS). The complexity of
neurodegeneration calls for large-scale unbiased screening studies. Over the past few years,
we have made breakthrough observations that have significant implications for the
understanding of cellular defense systems against proteotoxicity. Using a unique blend of
biochemical, genetic, and cell biological approaches, we discovered a novel pathway to
reprogram protein quality control, and with new genetic hits related to this pathway. Our work
has elucidated a previously unrecognized network in protein quality control. The studies on this
network could expand our understanding of proteotoxic-stress-responsive quality control
systems in the cell, beyond the well-established heat shock response or unfolded protein
response. The findings will suggest new strategies for harnessing the cellular defense system
to prevent and treat the relevant forms of neurodegenerative diseases associated with
proteotoxicity. Our project will be focused on investigating novel molecular targets that are
identified through unbiased screens and testing new small molecule compounds that have
been designed to be specific inhibitors of this target. We predict that the advances gained
through our research efforts will eventually lead to new therapeutic interventions to address the
relevant neurodegenerative diseases.

## Key facts

- **NIH application ID:** 10920047
- **Project number:** 1R41NS137860-01
- **Recipient organization:** REZIGENE, LLC
- **Principal Investigator:** Tao Zhang
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $349,854
- **Award type:** 1
- **Project period:** 2024-09-17 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10920047

## Citation

> US National Institutes of Health, RePORTER application 10920047, Developing an Anti-proteotoxicity Therapy for Neurodegenerative Diseases (1R41NS137860-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10920047. Licensed CC0.

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