| First Author | Miyagawa T | Year | 2016 |
| Journal | Hum Mol Genet | Volume | 25 |
| Issue | 14 | Pages | 2948-2958 |
| PubMed ID | 27179792 | Mgi Jnum | J:237310 |
| Mgi Id | MGI:5811968 | Doi | 10.1093/hmg/ddw146 |
| Citation | Miyagawa T, et al. (2016) BIN1 regulates BACE1 intracellular trafficking and amyloid-beta production. Hum Mol Genet 25(14):2948-2958 |
| abstractText | BIN1 is a genetic risk factor of late-onset Alzheimer disease (AD), which was identified in multiple genome-wide association studies. BIN1 is a member of the amphiphysin family of proteins, and contains N-terminal Bin-Amphiphysin-Rvs and C-terminal Src homology 3 domains. BIN1 is widely expressed in the mouse and human brains, and has been reported to function in the endocytosis and the endosomal sorting of membrane proteins. BACE1 is a type 1 transmembrane aspartyl protease expressed predominantly in neurons of the brain and responsible for the production of amyloid-beta peptide (Abeta). Here we report that the depletion of BIN1 increases cellular BACE1 levels through impaired endosomal trafficking and reduces BACE1 lysosomal degradation, resulting in increased Abeta production. Our findings provide a mechanistic role of BIN1 in the pathogenesis of AD as a novel genetic regulator of BACE1 levels and Abeta production. |
