| First Author | Yu H | Year | 2023 |
| Journal | Front Aging Neurosci | Volume | 15 |
| Pages | 1241750 | PubMed ID | 37771520 |
| Mgi Jnum | J:347834 | Mgi Id | MGI:7537715 |
| Doi | 10.3389/fnagi.2023.1241750 | Citation | Yu H, et al. (2023) The gamma-Adducin 1-357 fragment promotes tau pathology. Front Aging Neurosci 15:1241750 |
| abstractText | BACKGROUND: Tau phosphorylation is a pathological hallmark of Alzheimer's disease (AD). Previously, we reported that the gamma-adducin 1-357 fragment is present in the brains of AD patients. However, it remains unknown how gamma-adducin regulates tau phosphorylation. OBJECTIVE: The aim of this project is to investigate the effects of the gamma-adducin 1-357 fragment on tau phosphorylation and the kinases involved in this process. METHODS: Full-length gamma-adducin or the gamma-adducin 1-357 fragment was expressed in HEK293 cells, SH-SY5Y cells, and primary neurons. The phosphorylation of tau Ser396 was determined using Western blot and immunofluorescence. Tau P301S transgenic mice were injected with adeno-associated virus encoding full-length gamma-adducin or gamma-adducin 1-357 fragment to determine the phosphorylation of tau. RESULTS: The gamma-adducin 1-357 fragment enhances tau phosphorylation at Ser396. Additionally, the expression of the gamma-adducin 1-357 fragment leads to the activation of glycogen synthase kinase-3beta (GSK-3beta). This effect was mitigated by the GSK-3beta inhibitor 4-Benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione (TDZD-8). CONCLUSION: The gamma-adducin 1-357 fragment enhances tau phosphorylation by activating GSK3beta. These results support that the fragmentation of gamma-adducin may play a pivotal role in tau pathology. |
