Generation of aggregation prone N-terminally truncated amyloid β peptides by meprin β depends on the sequence specificity at the cleavage site
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Generation of aggregation prone N-terminally truncated amyloid β peptides by meprin β depends on the sequence specificity at the cleavage site. / Schönherr, Caroline; Bien, Jessica; Isbert, Simone; Wichert, Rielana; Prox, Johannes; Altmeppen, Hermann; Kumar, Sathish; Walter, Jochen; Lichtenthaler, Stefan F; Weggen, Sascha; Glatzel, Markus; Becker-Pauly, Christoph; Pietrzik, Claus U.
In: MOL NEURODEGENER, Vol. 11, No. 1, 19.02.2016, p. 19.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Generation of aggregation prone N-terminally truncated amyloid β peptides by meprin β depends on the sequence specificity at the cleavage site
AU - Schönherr, Caroline
AU - Bien, Jessica
AU - Isbert, Simone
AU - Wichert, Rielana
AU - Prox, Johannes
AU - Altmeppen, Hermann
AU - Kumar, Sathish
AU - Walter, Jochen
AU - Lichtenthaler, Stefan F
AU - Weggen, Sascha
AU - Glatzel, Markus
AU - Becker-Pauly, Christoph
AU - Pietrzik, Claus U
PY - 2016/2/19
Y1 - 2016/2/19
N2 - BACKGROUND: 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.RESULTS: 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).CONCLUSION: 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.
AB - BACKGROUND: 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.RESULTS: 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).CONCLUSION: 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.
U2 - 10.1186/s13024-016-0084-5
DO - 10.1186/s13024-016-0084-5
M3 - SCORING: Journal article
C2 - 26895626
VL - 11
SP - 19
JO - MOL NEURODEGENER
JF - MOL NEURODEGENER
SN - 1750-1326
IS - 1
ER -