# Role of Stress Granule Protein Aggregation in Axon Regeneration

> **NIH NIH R01** · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · 2021 · $75,738

## Abstract

Peripheral nerve injuries are common with more than 200,000 new cases reported each year in
the United States alone. Only about 10% of these individuals regain much function. Nerve injury
significantly impacts long-term quality of life, and most injured individuals seek continued
treatments for associated disabilities and pain. The most common explanation for poor
functional outcomes is the slow and inefficient process of axon regeneration. Proteins
synthesized locally in axons contribute to peripheral nerve regeneration by providing retrograde
signals for injury responses and supporting axon regrowth locally. We have shown that mRNAs
are stored in PNS axons in RNA-protein aggregates that contain the stress granule protein
G3BP1. G3BP1 protein can drive stress granule aggregation, and G3BP1 phosphorylation
blocks stress granule assembly. G3BP1 binds to mRNAs in axons and attenuates their
translation. We have discovered exogenous agents and endogenous signals that trigger
disassembly of axonal G3BP1 aggregates. The exogenous agents specifically increase axonal
protein synthesis and accelerate axon growth rates in vitro and in vivo. However, translational
regulation of axonal mRNAs has been demonstrated in models of neuropathic pain, and nerve
injury patients frequently seek additional treatment after peripheral nerve injury for the
development of neuropathic pain. Whether acute disassembly of G3BP1 RNAs within
nociceptive neurons will lead to or exacerbate neuropathic pain is unknown and is a key step
toward translatability of this type of therapy. This ‘Research Supplement to Promote Diversity in
Health-Related Research’ is designed to bring translational research experience to a post-
baccalaureate fellow with mentoring from a team of one junior and two senior investigators.
This will prepare the fellow for graduate school and strengthen her applications.

## Key facts

- **NIH application ID:** 10406395
- **Project number:** 3R01NS117821-02S1
- **Recipient organization:** UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA
- **Principal Investigator:** JEFFERY L TWISS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $75,738
- **Award type:** 3
- **Project period:** 2020-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10406395

## Citation

> US National Institutes of Health, RePORTER application 10406395, Role of Stress Granule Protein Aggregation in Axon Regeneration (3R01NS117821-02S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10406395. Licensed CC0.

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