| First Author | Shi Z | Year | 2017 |
| Journal | Biochim Biophys Acta | Volume | 1863 |
| Issue | 9 | Pages | 2398-2407 |
| PubMed ID | 28502705 | Mgi Jnum | J:251833 |
| Mgi Id | MGI:6104651 | Doi | 10.1016/j.bbadis.2017.05.014 |
| Citation | Shi Z, et al. (2017) BAG-1M co-activates BACE1 transcription through NF-kappaB and accelerates Abeta production and memory deficit in Alzheimer's disease mouse model. Biochim Biophys Acta 1863(9):2398-2407 |
| abstractText | Accumulation of amyloid beta protein (Abeta)-containing neuritic plaques in the brain is a neuropathological feature of Alzheimer''s disease (AD). The beta-site APP-cleaving enzyme 1 (BACE1) is essential for Abeta generation and dysregulation of BACE1 expression may lead to AD pathogenesis. Bcl-2-associated athanogen 1M (BAG-1M), initially identified as an anti-apoptotic protein, has also been found to be highly expressed in the same neurons that contain intracellular amyloid in the hippocampus of AD patient. In this report, we found that over-expression of BAG-1M enhances BACE1-mediated cleavage of amyloid precursor protein (APP) and Abeta production by up-regulating BACE1 gene transcription. The regulation of BACE1 transcription by BAG-1M was dependent on NF-kappaB, as BAG-1M complexes NF-kappaB at the promoter of BACE1 gene and co-activates NF-kappaB-facilitated BACE1 transcription. Moreover, expression of BAG-1M by lentiviral vector in the hippocampus of AD transgenic model mice promotes Abeta generation and formation of neuritic plaque, and subsequently accelerates memory deficits of the mice. These results provide evidence for an emerging role of BAG-1M in the regulation of BACE1 expression and AD pathogenesis and that targeting the BAG-1M-NF-kappaB complex may provide a mechanism for inhibiting Abeta production and plaque formation. |
