R01AG072430
Project Grant
Overview
Grant Description
Mitigating Neuroinflammation and Enhancing Neuronal Integrity in Alzheimer's Disease - 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:
1. How does MG53 contribute to the maintenance of neural integrity associated with the progression of AD?
2. What are the mechanisms that underlie MG53's anti-inflammation function in the microglia?
3. Can we target the dual function of MG53 as a means for alleviation of neurodegeneration associated with the progression of AD?
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:
1. How does MG53 contribute to the maintenance of neural integrity associated with the progression of AD?
2. What are the mechanisms that underlie MG53's anti-inflammation function in the microglia?
3. Can we target the dual function of MG53 as a means for alleviation of neurodegeneration associated with the progression of AD?
Funding Goals
NOT APPLICABLE
Grant Program (CFDA)
Awarding / Funding Agency
Place of Performance
Virginia
United States
Geographic Scope
State-Wide
Related Opportunity
Analysis Notes
Amendment Since initial award the total obligations have increased 398% from $688,260 to $3,426,464.
Rector & Visitors Of The University Of Virginia was awarded
Neuroinflammation Mitigation with MG53: A Novel Approach Alzheimer's Disease
Project Grant R01AG072430
worth $3,426,464
from National Institute on Aging in September 2022 with work to be completed primarily in Virginia United States.
The grant
has a duration of 4 years 9 months and
was awarded through assistance program 93.866 Aging Research.
The Project Grant was awarded through grant opportunity Research on Current Topics in Alzheimer's Disease and Its Related Dementias (R01 Clinical Trial Optional).
Status
(Ongoing)
Last Modified 7/6/26
Period of Performance
9/30/22
Start Date
6/30/27
End Date
Funding Split
$3.4M
Federal Obligation
$0.0
Non-Federal Obligation
$3.4M
Total Obligated
Activity Timeline
Transaction History
Modifications to R01AG072430
Additional Detail
Award ID FAIN
R01AG072430
SAI Number
R01AG072430-2813895116
Award ID URI
SAI UNAVAILABLE
Awardee Classifications
Public/State Controlled Institution Of Higher Education
Awarding Office
75NN00 NIH National Insitute on Aging
Funding Office
75NN00 NIH National Insitute on Aging
Awardee UEI
JJG6HU8PA4S5
Awardee CAGE
9B982
Performance District
VA-90
Senators
Mark Warner
Timothy Kaine
Timothy Kaine
Budget Funding
| Federal Account | Budget Subfunction | Object Class | Total | Percentage |
|---|---|---|---|---|
| National Institute on Aging, National Institutes of Health, Health and Human Services (075-0843) | Health research and training | Grants, subsidies, and contributions (41.0) | $1,376,413 | 100% |
Modified: 7/6/26