Abstract
Alzheimer’s Disease (AD) is the most common neurodegenerative disease that involves neuronal cell death initiated by the breakdown of the plasma membrane. Amyloid beta (Aβ), a hallmark protein that contributes to AD pathogenesis, is known to interact directly with the plasma membrane and induce increased intracellular calcium levels, reactive oxygen species (ROS), and cell death. Our recent studies revealed that elevated levels of Aβ42 induce a plasma membrane repair defect in neurons that compromises this conserved cellular response that would normally repair the disruption. Here, we tested if recombinant MG53/TRIM72 protein (rhMG53), a therapeutic protein known to increase plasma membrane repair capacity, could enhance membrane repair in AD neurons. rhMG53 increased plasma membrane repair in ex vivo and in vitro tissue treated with Aβ42 or cerebrospinal fluid from AD patients, normalizing intracellular calcium levels, ROS, and cell death in treated cells. This study demonstrates that increasing plasma membrane repair can rescue neural cells from the neurotoxic effects of Aβ, indicating that elevating plasma membrane repair could be a viable therapeutic approach to reduce neuronal death in AD.
| Original language | English |
|---|---|
| Article number | 418 |
| Journal | Biomolecules |
| Volume | 15 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 2025 |
Bibliographical note
Publisher Copyright:© 2025 by the authors.
Funding
Research reported in this publication was supported by the National Institute on Aging of the National Institutes of Health under award number R01AG056504. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The research presented in this publication was also supported in part by the Jain Foundation, The Ohio State University College of Medicine Office of Research Dean\u2019s Discovery Funding Program under award number GF305835, The Ohio State University Department of Physiology and Cell Biology Nishikawara Student Research Grant, The Ohio State University CTSI Spark Award, and NIH T32 AG078110 training grant \u201CTraining in Translational Research in Alzheimer\u2019s and Related Dementias (TRIAD)\u201D. Images were generated at The Ohio State University Campus Microscopy and Imaging Facility, which is supported in part by grant P30 CA016058, National Cancer Institute, Bethesda, Maryland, USA. Patient samples were provided by The Ohio State University Neuroscience Research Institute Biobank and Biorepository, Columbus, OH, USA.
| Funders | Funder number |
|---|---|
| “Training in Translational Research in Alzheimer’s and Related Dementias (TRIAD | |
| Ohio State University Department of Physiology and Cell Biology Nishikawara Student Research | |
| Jain Foundation | |
| Ohio Water Resources Center, Ohio State University | |
| National Childhood Cancer Registry – National Cancer Institute | |
| Triad National Security | |
| National Institute on Aging | |
| National Institutes of Health (NIH) | R01AG056504, T32 AG078110 |
| National Institutes of Health (NIH) | |
| College of Medicine Office of Research, Ohio State University | GF305835 |
| College of Medicine Office of Research, Ohio State University |
Keywords
- Alzheimer’s disease
- neurotoxicity
- plasma membrane repair
- protein therapeutics
- rhMG53
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology