| First Author | Liu XH | Year | 2015 |
| Journal | Neurobiol Dis | Volume | 74 |
| Pages | 377-91 | PubMed ID | 25484286 |
| Mgi Jnum | J:348511 | Mgi Id | MGI:6140802 |
| Doi | 10.1016/j.nbd.2014.11.020 | Citation | Liu XH, et al. (2015) Blocking GSK3beta-mediated dynamin1 phosphorylation enhances BDNF-dependent TrkB endocytosis and the protective effects of BDNF in neuronal and mouse models of Alzheimer's disease. Neurobiol Dis 74:377-91 |
| abstractText | Endocytosis of tropomyosin related kinase B (TrkB) receptors has critical roles in brain-derived neurotrophic factor (BDNF) mediated signal transduction and biological function, however the mechanism that is governing TrkB endocytosis is still not completely understood. In this study, we showed that GSK3beta, a key kinase in neuronal development and survival, could regulate TrkB endocytosis through phosphorylating dynamin1 (Dyn1) but not dynamin2 (Dyn2). Moreover, we found that beta-amyloid (Abeta) oligomer exposure could impair BDNF-dependent TrkB endocytosis and Akt activation through enhancing GSK3beta activity in cultured hippocampal neurons, which suggested that BDNF-induced TrkB endocytosis and the subsequent signaling were impaired in neuronal model of Alzheimer''s disease (AD). Notably, we found that inhibiting GSK3beta phosphorylating Dyn1 by using TAT-Dyn1SpS could rescue the impaired TrkB endocytosis and Akt activation upon BDNF stimuli under Abeta exposure. Finally, TAT-Dyn1SpS could facilitate BDNF-mediated neuronal survival and cognitive enhancement in mouse models of AD. These results clarified a role of GSK3beta in BDNF-dependent TrkB endocytosis and the subsequent signaling, and provided a potential new strategy by inhibiting GSK3beta-induced Dyn1 phosphorylation for AD treatment. |
