| First Author | Bulgart HR | Year | 2024 |
| Journal | FASEB J | Volume | 38 |
| Issue | 20 | Pages | e70099 |
| PubMed ID | 39400395 | Mgi Jnum | J:359569 |
| Mgi Id | MGI:7787170 | Doi | 10.1096/fj.202401731RR |
| Citation | Bulgart HR, et al. (2024) Plasma membrane repair defect in Alzheimer's disease neurons is driven by the reduced dysferlin expression. FASEB J 38(20):e70099 |
| abstractText | Alzheimer's disease (AD) is the most common neurodegenerative disease, and a defect in neuronal plasma membrane repair could exacerbate neurotoxicity, neuronal death, and disease progression. In this study, application of AD patient cerebrospinal fluid (CSF) and recombinant human Abeta to otherwise healthy neurons induces defective neuronal plasma membrane repair in vitro and ex vivo. We identified Abeta as the biochemical component in patient CSF leading to compromised repair capacity and depleting Abeta rescued repair capacity. These elevated Abeta levels reduced expression of dysferlin, a protein that facilitates membrane repair, by altering autophagy and reducing dysferlin trafficking to sites of membrane injury. Overexpression of dysferlin and autophagy inhibition rescued membrane repair. Overall, these findings indicate an AD pathogenic mechanism where Abeta impairs neuronal membrane repair capacity and increases susceptibility to cell death. This suggests that membrane repair could be therapeutically targeted in AD to restore membrane integrity and reduce neurotoxicity and neuronal death. |
