Matches in SemOpenAlex for { <https://semopenalex.org/work/W2048284889> ?p ?o ?g. }
Showing items 1 to 90 of
90
with 100 items per page.
- W2048284889 abstract "Presenilins (PS) contain the most frequently observed FAD associated mutations. There are now more than one hundred PS mutations described which probably all cause early onset AD by a subtle shift of the cleavage of betaAPP within its membrane from position 40 to position 42 of Abeta. The exact molecular mechanism behind this shift in cleavage precision is currently unclear. PS, signal peptide peptidase (SPP) and the SPP-like proteases (SPPL2a, SPPL2b, and SPPL3) share a common active site motif within transmembrane domain 7, the GxGD motif, defining the novel class of GxGD-type intramembrane cleaving aspartyl proteases. Unlike gamma-secretase, where numerous substrates have been identified, only three substrates for the SPP-family are known. These are TNFα 1, Bri2 (Itm2b) 2 and the Fas-Ligand. Mass spectrometry, radiosequencing, western blot analysis, immunoprecipitation. We have introduced the FAD-associated PS1 G384A mutation, occurring at the glycine N-terminal of the critical aspartate in TM7 of PS1, into the homologous and highly conserved GxGD-motif of SPPL2b and investigated the production of TNFα ICD species. Surprisingly, the mutation in SPPL2b results in the generation of a longer intracellular cleavage product of TNFα, which was produced by a slowed sequential cleavage within the membrane. Since the N-termini of the secreted counterparts remained unchanged, the mutation selectively affects the liberation of the intracellular processing products. These findings are consistent with a model that suggests that at least aggressive FAD associated PS mutations result in a reduced function, which slows sequential intramembrane proteolysis and thus over time results in the accumulation of Aβ42." @default.
- W2048284889 created "2016-06-24" @default.
- W2048284889 creator A5006277000 @default.
- W2048284889 creator A5017314590 @default.
- W2048284889 creator A5022068141 @default.
- W2048284889 creator A5056375133 @default.
- W2048284889 creator A5065084452 @default.
- W2048284889 creator A5079758598 @default.
- W2048284889 date "2008-07-01" @default.
- W2048284889 modified "2023-09-27" @default.
- W2048284889 title "P4-188: Intramembrane cleavage of TNFalpha by SPPL2b carrying a familial Alzheimer's disease-like mutation" @default.
- W2048284889 cites W1544986395 @default.
- W2048284889 cites W2021937623 @default.
- W2048284889 doi "https://doi.org/10.1016/j.jalz.2008.05.2255" @default.
- W2048284889 hasPublicationYear "2008" @default.
- W2048284889 type Work @default.
- W2048284889 sameAs 2048284889 @default.
- W2048284889 citedByCount "0" @default.
- W2048284889 crossrefType "journal-article" @default.
- W2048284889 hasAuthorship W2048284889A5006277000 @default.
- W2048284889 hasAuthorship W2048284889A5017314590 @default.
- W2048284889 hasAuthorship W2048284889A5022068141 @default.
- W2048284889 hasAuthorship W2048284889A5056375133 @default.
- W2048284889 hasAuthorship W2048284889A5065084452 @default.
- W2048284889 hasAuthorship W2048284889A5079758598 @default.
- W2048284889 hasConcept C104317684 @default.
- W2048284889 hasConcept C118892022 @default.
- W2048284889 hasConcept C142724271 @default.
- W2048284889 hasConcept C151730666 @default.
- W2048284889 hasConcept C153911025 @default.
- W2048284889 hasConcept C170493617 @default.
- W2048284889 hasConcept C175156509 @default.
- W2048284889 hasConcept C175344181 @default.
- W2048284889 hasConcept C181199279 @default.
- W2048284889 hasConcept C182220744 @default.
- W2048284889 hasConcept C185592680 @default.
- W2048284889 hasConcept C24530287 @default.
- W2048284889 hasConcept C2779134260 @default.
- W2048284889 hasConcept C2781307694 @default.
- W2048284889 hasConcept C43369102 @default.
- W2048284889 hasConcept C502032728 @default.
- W2048284889 hasConcept C515207424 @default.
- W2048284889 hasConcept C55493867 @default.
- W2048284889 hasConcept C71829478 @default.
- W2048284889 hasConcept C71924100 @default.
- W2048284889 hasConcept C79879829 @default.
- W2048284889 hasConcept C86803240 @default.
- W2048284889 hasConcept C95444343 @default.
- W2048284889 hasConceptScore W2048284889C104317684 @default.
- W2048284889 hasConceptScore W2048284889C118892022 @default.
- W2048284889 hasConceptScore W2048284889C142724271 @default.
- W2048284889 hasConceptScore W2048284889C151730666 @default.
- W2048284889 hasConceptScore W2048284889C153911025 @default.
- W2048284889 hasConceptScore W2048284889C170493617 @default.
- W2048284889 hasConceptScore W2048284889C175156509 @default.
- W2048284889 hasConceptScore W2048284889C175344181 @default.
- W2048284889 hasConceptScore W2048284889C181199279 @default.
- W2048284889 hasConceptScore W2048284889C182220744 @default.
- W2048284889 hasConceptScore W2048284889C185592680 @default.
- W2048284889 hasConceptScore W2048284889C24530287 @default.
- W2048284889 hasConceptScore W2048284889C2779134260 @default.
- W2048284889 hasConceptScore W2048284889C2781307694 @default.
- W2048284889 hasConceptScore W2048284889C43369102 @default.
- W2048284889 hasConceptScore W2048284889C502032728 @default.
- W2048284889 hasConceptScore W2048284889C515207424 @default.
- W2048284889 hasConceptScore W2048284889C55493867 @default.
- W2048284889 hasConceptScore W2048284889C71829478 @default.
- W2048284889 hasConceptScore W2048284889C71924100 @default.
- W2048284889 hasConceptScore W2048284889C79879829 @default.
- W2048284889 hasConceptScore W2048284889C86803240 @default.
- W2048284889 hasConceptScore W2048284889C95444343 @default.
- W2048284889 hasIssue "4S_Part_22" @default.
- W2048284889 hasLocation W20482848891 @default.
- W2048284889 hasOpenAccess W2048284889 @default.
- W2048284889 hasPrimaryLocation W20482848891 @default.
- W2048284889 hasRelatedWork W1967408738 @default.
- W2048284889 hasRelatedWork W1986049708 @default.
- W2048284889 hasRelatedWork W1986443184 @default.
- W2048284889 hasRelatedWork W1988923764 @default.
- W2048284889 hasRelatedWork W2031055724 @default.
- W2048284889 hasRelatedWork W2056790763 @default.
- W2048284889 hasRelatedWork W2065129254 @default.
- W2048284889 hasRelatedWork W2126770730 @default.
- W2048284889 hasRelatedWork W2152926110 @default.
- W2048284889 hasRelatedWork W3006246158 @default.
- W2048284889 hasVolume "4" @default.
- W2048284889 isParatext "false" @default.
- W2048284889 isRetracted "false" @default.
- W2048284889 magId "2048284889" @default.
- W2048284889 workType "article" @default.