# Mitigating neuroinflammation and enhancing neuronal integrity in Alzheimer's disease

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 2024 · $688,045

## Abstract

Project Summary
Alzheimer's disease (AD) is an age-dependent neurodegenerative disorder associated with chronic
neuroinflammation and the build-up of amyloid plaques and neurofibrillary tangles in the brain. A therapeutic
approach that harnesses neuroinflammation and restores neuronal integrity can potentially be an effective
means to alleviate the progression of neurodegeneration in AD. Here we provide novel findings supporting the
notion that MG53, a tissue repair protein, can potentially slow AD neurodegeneration by protecting neurons from
stress-induced injuries and mitigating neuroinflammation associated with AD. MG53 is a member of the TRIM
protein family that plays an essential role in cell membrane repair. While predominantly expressed in skeletal
muscle, moderate exercise can induce secretion of MG53 into circulation to elicit its tissue protective function.
Transgenic mice with increased levels of MG53 in the bloodstream live a healthy lifespan and are resistant to
stress-induced brain injury. Recombinant human MG53 (rhMG53) protein, administered systemically, can
permeate the blood-brain barrier (BBB) to protect against traumatic brain injuries (TBI) in rodents and pigs. MG53
also passes through the BBB of human AD patients as it is detected in cerebrospinal fluid. In addition to
facilitating tissue repair, MG53 has an anti-inflammation function that dampens neuroinflammation associated
with TBI and LPS-neurotoxicity in mice. Pilot studies with AD mice reveal beneficial effects of rhMG53 to
enhance neuronal integrity and reduce neuroinflammation through control of microglia activation. The long-
term goal of this project is to decipher the physiology of MG53 in neuroprotection and to translate the basic
findings into a clinical treatment for AD. We have assembled a team with complementary expertise in
neurophysiology, microglia biology, innovative live-cell imaging, clinical AD research and unique animal models
of AD, with the goal to arrive at a mechanistic understanding of MG53's dual function in control of
neuroinflammation and in preservation of neuronal integrity during AD progression. The experiments designed
in this proposal are focused on addressing the following three fundamental questions: How does MG53
contribute to the maintenance of neural integrity associated with the progression of AD? What are the
mechanisms that underlie MG53's anti-inflammation function in the microglia? Can we target the dual function
of MG53 as a means for alleviation of neurodegeneration associated with the progression of AD?

## Key facts

- **NIH application ID:** 10873859
- **Project number:** 5R01AG072430-03
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Jianjie Ma
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $688,045
- **Award type:** 5
- **Project period:** 2022-09-30 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10873859

## Citation

> US National Institutes of Health, RePORTER application 10873859, Mitigating neuroinflammation and enhancing neuronal integrity in Alzheimer's disease (5R01AG072430-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10873859. Licensed CC0.

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