Title |
Generation of aggregation prone N-terminally truncated amyloid β peptides by meprin β depends on the sequence specificity at the cleavage site
|
---|---|
Published in |
Molecular Neurodegeneration, February 2016
|
DOI | 10.1186/s13024-016-0084-5 |
Pubmed ID | |
Authors |
Caroline Schönherr, Jessica Bien, Simone Isbert, Rielana Wichert, Johannes Prox, Hermann Altmeppen, Sathish Kumar, Jochen Walter, Stefan F. Lichtenthaler, Sascha Weggen, Markus Glatzel, Christoph Becker-Pauly, Claus U. Pietrzik |
Abstract |
The metalloprotease meprin β cleaves the Alzheimer's Disease (AD) relevant amyloid precursor protein (APP) as a β-secretase reminiscent of BACE-1, however, predominantly generating N-terminally truncated Aβ2-x variants. Herein, we observed increased endogenous sAPPα levels in the brains of meprin β knock-out (ko) mice compared to wild-type controls. We further analyzed the cellular interaction of APP and meprin β and found that cleavage of APP by meprin β occurs prior to endocytosis. The N-terminally truncated Aβ2-40 variant shows increased aggregation propensity compared to Aβ1-40 and acts even as a seed for Aβ1-40 aggregation. Additionally, we observed that different APP mutants affect the catalytic properties of meprin β and that, interestingly, meprin β is unable to generate N-terminally truncated Aβ peptides from Swedish mutant APP (APPswe). Concluding, we propose that meprin β may be involved in the generation of N-terminally truncated Aβ2-x peptides of APP, but acts independently from BACE-1. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Russia | 1 | 2% |
Unknown | 60 | 98% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 11 | 18% |
Student > Doctoral Student | 9 | 15% |
Student > Master | 8 | 13% |
Student > Bachelor | 4 | 7% |
Researcher | 4 | 7% |
Other | 7 | 11% |
Unknown | 18 | 30% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 13 | 21% |
Biochemistry, Genetics and Molecular Biology | 9 | 15% |
Neuroscience | 7 | 11% |
Chemistry | 4 | 7% |
Medicine and Dentistry | 4 | 7% |
Other | 4 | 7% |
Unknown | 20 | 33% |