| First Author | Schönherr C | Year | 2016 |
| Journal | Mol Neurodegener | Volume | 11 |
| Pages | 19 | PubMed ID | 26895626 |
| Mgi Jnum | J:285078 | Mgi Id | MGI:6393063 |
| Doi | 10.1186/s13024-016-0084-5 | Citation | Schonherr C, et al. (2016) Generation of aggregation prone N-terminally truncated amyloid beta peptides by meprin beta depends on the sequence specificity at the cleavage site. Mol Neurodegener 11:19 |
| abstractText | BACKGROUND: The metalloprotease meprin beta cleaves the Alzheimer's Disease (AD) relevant amyloid precursor protein (APP) as a beta-secretase reminiscent of BACE-1, however, predominantly generating N-terminally truncated Abeta2-x variants. RESULTS: Herein, we observed increased endogenous sAPPalpha levels in the brains of meprin beta knock-out (ko) mice compared to wild-type controls. We further analyzed the cellular interaction of APP and meprin beta and found that cleavage of APP by meprin beta occurs prior to endocytosis. The N-terminally truncated Abeta2-40 variant shows increased aggregation propensity compared to Abeta1-40 and acts even as a seed for Abeta1-40 aggregation. Additionally, we observed that different APP mutants affect the catalytic properties of meprin beta and that, interestingly, meprin beta is unable to generate N-terminally truncated Abeta peptides from Swedish mutant APP (APPswe). CONCLUSION: Concluding, we propose that meprin beta may be involved in the generation of N-terminally truncated Abeta2-x peptides of APP, but acts independently from BACE-1. |
