# Neuromuscular junction regeneration

> **NIH VA I01** · LOUIS STOKES CLEVELAND VA MEDICAL CENTER · 2022 · —

## Abstract

The long term goal of our study is to understand mechanisms underlying functional recovery from
muscle and nerve injuries. In this proposal we will focus on regeneration of the neuromuscular
junction (NMJ). The NMJ is a synapse that transmits signals from motor neurons to muscle fibers
to control muscle contraction. Skeletal muscle and peripheral nerve injuries are common among
soldiers in non-battle related activities such as exercise. Their incident rate increases significantly
during war time. In fact, extremity injuries account for the majority of combat wounds.
Unavoidably, the NMJ becomes damaged in skeletal muscle and peripheral nerve injuries. In
addition, muscles become denervated in various peripheral neurodegenerative disorders like
amyotrophic lateral sclerosis, Duchenne-Aran muscular atrophy and progressive bulbar palsy,
many of which affect veterans more than the general population. Recovery from muscle/nerve
injuries and peripheral neurodegenerative disorders requires nerve regrowth, muscle repair and in
particular NMJ regeneration, a process by which denervated muscles become reinnervated by
motor nerves. However, unlike nerve and muscle repair/regeneration, much less is known about
molecular mechanisms of reinnervation of injury muscles, which is a glaring gap in our
understanding of functional recovery from muscle/nerve injury. Consequently, therapeutic
interventions to promote NMJ regeneration are limited. Recent studies have revealed critical
mechanisms for NMJ assembly and maintenance. Evidence indicates that the agrin signaling is
not only important for NMJ formation, but also necessary for its maintenance. These advances
provide a niche to study mechanisms of NMJ regeneration. In this proposal, we will test the
hypotheses that agrin signaling is critical for NMJ regeneration after injury and that increasing
agrin signaling promotes NMJ regeneration. The results will provide a better understanding of
agrin signaling in NMJ regeneration, a prerequisite to developing better therapeutic intervention
for muscle/nerve injury from combat wounds and peripheral neurological disorders that occur at
higher rates among veterans.

## Key facts

- **NIH application ID:** 10296649
- **Project number:** 5I01BX001020-08
- **Recipient organization:** LOUIS STOKES CLEVELAND VA MEDICAL CENTER
- **Principal Investigator:** Lin Mei
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2013-10-01 → 2023-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10296649

## Citation

> US National Institutes of Health, RePORTER application 10296649, Neuromuscular junction regeneration (5I01BX001020-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10296649. Licensed CC0.

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