| First Author | Feng T | Year | 2016 |
| Journal | Mol Neurobiol | Volume | 53 |
| Issue | 6 | Pages | 3690-3701 |
| PubMed ID | 26115702 | Mgi Jnum | J:315121 |
| Mgi Id | MGI:6830319 | Doi | 10.1007/s12035-015-9306-z |
| Citation | Feng T, et al. (2016) SNX15 Regulates Cell Surface Recycling of APP and Abeta Generation. Mol Neurobiol 53(6):3690-3701 |
| abstractText | Amyloid-beta (Abeta) peptide plays an essential role in the pathogenesis of Alzheimer's disease (AD) and is generated from amyloid-beta precursor protein (APP) through sequential proteolytic cleavages by beta-site APP cleaving enzyme 1 (BACE1) and gamma-secretase. Trafficking dysregulation of APP, BACE1, and gamma-secretase may affect Abeta generation and disease pathogenesis. Sorting nexin 15 (SNX15) is known to regulate protein trafficking. Here, we report that SNX15 is abundantly expressed in mouse neurons and astrocytes. In addition, we show that although not affecting the protein levels of APP, BACE1, and gamma-secretase components and the activity of BACE1 and gamma-secretase, overexpression and downregulation of SNX15 reduce and promote Abeta production, respectively. Furthermore, we find that overexpression of SNX15 increases APP protein levels in cell surface through accelerating APP recycling, whereas downregulation of SNX15 has an opposite effect. Finally, we show that exogenous expression of human SNX15 in the hippocampal dentate gyrus by adeno-associated virus (AAV) infection can significantly reduce Abeta pathology in the hippocampus and improve short-term working memory in the APPswe/PSEN1dE9 double transgenic AD model mice. Together, our results suggest that SNX15 regulates the recycling of APP to cell surface and, thus, its processing for Abeta generation. |
