# Neurodegeneration and Proteotoxicity Dissected in C. elegans and Mammals

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2020 · $364,973

## Abstract

Project Summary
 Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease
characterized by the degeneration of motor neurons. Protein misfolding and aggregation are a
central feature of ALS and related neurodegenerative diseases. 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 in hand. We
now propose work to elucidate a previously unrecognized p53 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. Our unique potential to contribute to this field is both technical and
conceptual: We have developed a unique tandem C. elegans/mammalian system to study
neurodegeneration, and our recent success bodes well for future plans. For example, our
expanding repertoire of diease models will allow us to conduct unbiased screening studies of
proteotoxicity-associated neurodegeneration in vivo and extend the findings to mammalian
models and patient cells. The findings will not only provide novel entry points for understanding
the molecular causes of key ALS genes but also suggest new strategies for harnessing the
cellular defense system to prevent and treat the relevant forms of ALS and other related
neurodegenerative diseases. We predict that the advances gained through our research efforts
will eventually lead to new therapeutic interventions to address these diseases in the world's
rapidly aging population.

## Key facts

- **NIH application ID:** 9858444
- **Project number:** 5R01NS074324-10
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Jiou Wang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $364,973
- **Award type:** 5
- **Project period:** 2011-08-15 → 2021-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9858444

## Citation

> US National Institutes of Health, RePORTER application 9858444, Neurodegeneration and Proteotoxicity Dissected in C. elegans and Mammals (5R01NS074324-10). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/9858444. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*