# Evaluating Protein Quality Control in the Toxicity of TDP43 Fragments Associated with ALS and FTD

> **NIH NIH R15** · TEXAS WOMAN'S UNIVERSITY · 2022 · $72,067

## Abstract

Project Summary
People are living longer, which increases their risk of developing neurodegenerative disorders. Such
disorders can be characterized by the accumulation and aggregation of specific proteins in the brain.
These aggregates often contain protein fragments produced by increases in protein cleavage or
defects in protein quality control systems such as regulated protein degradation. Our overall goal is to
understand the effects of protein aggregates on normal cell function and to identify cellular pathways
that prevent toxicity. Previously we found that the N-termini of fragments associated with
neurodegenerative disorders influence their metabolism, tendency to aggregate, and the morphology
of their aggregates. We also reported that specific fragments of the TAR DNA Binding Protein 43
(TDP43) could be degraded either by the N-degron pathway or through a Bcl-2-associated
athanogene 6 (BAG6)-mediated fashion depending upon the extent of fragment hydrophobicity. The
studies proposed in this supplement will evaluate the level of cooperativity between BAG6 and the N-
degron pathway to protect cells from intracellular aggregation associated with neurodegeneration. It
will also examine whether this cooperatively results in the triaged removal of toxic proteins. This will
provide novel insight into how cells are protected from toxicity associated with neurodegeneration.
Finally, this sub-project is proposed as a Diversity Supplement to expand Aim 1 of the Parent R15
and to serve as a training vehicle for graduate student Winnie Lokuso.

## Key facts

- **NIH application ID:** 10571257
- **Project number:** 3R15NS095317-02A1S1
- **Recipient organization:** TEXAS WOMAN'S UNIVERSITY
- **Principal Investigator:** Christopher Scott Brower
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $72,067
- **Award type:** 3
- **Project period:** 2022-04-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10571257

## Citation

> US National Institutes of Health, RePORTER application 10571257, Evaluating Protein Quality Control in the Toxicity of TDP43 Fragments Associated with ALS and FTD (3R15NS095317-02A1S1). Retrieved via AI Analytics 2026-06-02 from https://api.ai-analytics.org/grant/nih/10571257. Licensed CC0.

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