First Author | Wang L | Year | 2017 |
Journal | Neurosci Lett | Volume | 661 |
Pages | 63-70 | PubMed ID | 28964771 |
Mgi Jnum | J:252534 | Mgi Id | MGI:6093601 |
Doi | 10.1016/j.neulet.2017.09.055 | Citation | Wang L, et al. (2017) The cytoplasmic nuclear shuttling of Beclin 1 in neurons with Alzheimer's disease-like injury. Neurosci Lett 661:63-70 |
abstractText | The abnormal expression of the autophagy-related protein Beclin 1 has been implicated in Alzheimer's disease (AD) brains, whereas the precise involvement of Caspase-mediated Beclin 1 cleavage in AD neurons has not yet been fully clarified. In this study, we investigated the distribution of Beclin 1 fragments in neurons with AD-like injury. Our results demonstrated that Beclin 1 was expressed in neurons but not in astrocytes in both neuron-glia co-cultures and in cortical tissue slices. The full length and C-terminal fragments of human Beclin 1 was mainly expressed in cytoplasm, while the N-terminal fragment of Beclin 1 was predominantly localized in nucleus. Compared to amyloid-beta (Abeta)42-1 treatment control, exposure of PC12 cells or cortical neurons to Abeta1-42 resulted in cell injury, with the appearance of neuritic shortening, reduced nuclear diameter in PC12 cells, beading formation and fragmentation in cortical neurons. A partial nuclear translocation of Beclin 1 was detected in cells incubated with Abeta1-42, which could be inhibited by the administration of pan-Caspase inhibitor or Caspase 3 specific inhibitor. Moreover, Beclin 1 mutation at 146/149 sites was resistant to Abeta1-42-induced nuclear translocation. The nuclear translocation of Beclin 1 could also been detected in the brains of 12-month-old APP(Swe)/PS1(dE9) transgenic mice. Our findings suggest that after Caspase 3-mediated Beclin 1 cleavage at 146/149 sites, the N-terminal fragments of Beclin 1 may partially translocate into nuclei in neurons subjected to AD-like injury. |