FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2024668488> ?p ?o ?g. }

• W2024668488 abstract "Understanding the substrate recognition mechanism of γ-secretase is a key step for establishing substrate-specific inhibition of amyloid β-protein (Aβ) production. However, it is widely believed that γ-secretase is a promiscuous protease and that its substrate-specific inhibition is elusive. Here we show that γ-secretase distinguishes the ectodomain length of substrates and preferentially captures and cleaves substrates containing a short ectodomain. We also show that a subset of peptides containing the CDCYCxxxxCxCxSC motif binds to the amino terminus of C99 and inhibits Aβ production in a substrate-specific manner. Interestingly, these peptides suppress β-secretase-dependent cleavage of APP, but not that of sialyltransferase 1. Most importantly, intraperitoneal administration of peptides into mice results in a significant reduction in cerebral Aβ levels. This report provides direct evidence of the substrate preference of γ-secretase and its mechanism. Our results demonstrate that the ectodomain of C99 is a potent target for substrate-specific anti-Aβ therapeutics to combat Alzheimer’s disease. γ-Secretase inhibitors are studied for their potential to treat Alzheimer’s disease, but their use is limited by side effects. Funamoto et al.show that γ-secretase preferentially cleaves substrates with short ectodomains and that inhibitors based on these ectodomains reduce disease-like pathology in mice." @default.
• W2024668488 created "2016-06-24" @default.
• W2024668488 creator A5010518835 @default.
• W2024668488 creator A5013301564 @default.
• W2024668488 creator A5016024085 @default.
• W2024668488 creator A5023317571 @default.
• W2024668488 creator A5029219248 @default.
• W2024668488 creator A5037301114 @default.
• W2024668488 creator A5049588162 @default.
• W2024668488 creator A5052948447 @default.
• W2024668488 creator A5056711785 @default.
• W2024668488 creator A5070254459 @default.
• W2024668488 creator A5074965642 @default.
• W2024668488 creator A5088700318 @default.
• W2024668488 date "2013-10-09" @default.
• W2024668488 modified "2023-10-16" @default.
• W2024668488 title "Substrate ectodomain is critical for substrate preference and inhibition of γ-secretase" @default.
• W2024668488 cites W1483703465 @default.
• W2024668488 cites W1502820594 @default.
• W2024668488 cites W1534001036 @default.
• W2024668488 cites W1567490604 @default.
• W2024668488 cites W1595935608 @default.
• W2024668488 cites W1626267121 @default.
• W2024668488 cites W1655404681 @default.
• W2024668488 cites W1963904512 @default.
• W2024668488 cites W1970055334 @default.
• W2024668488 cites W1974023102 @default.
• W2024668488 cites W1977688919 @default.
• W2024668488 cites W1978285772 @default.
• W2024668488 cites W1986443184 @default.
• W2024668488 cites W1989453114 @default.
• W2024668488 cites W1993722622 @default.
• W2024668488 cites W1994379399 @default.
• W2024668488 cites W2003239559 @default.
• W2024668488 cites W2003659505 @default.
• W2024668488 cites W2011424449 @default.
• W2024668488 cites W2013306109 @default.
• W2024668488 cites W2017917068 @default.
• W2024668488 cites W2018647432 @default.
• W2024668488 cites W2023274935 @default.
• W2024668488 cites W2028493269 @default.
• W2024668488 cites W2034766896 @default.
• W2024668488 cites W2037083628 @default.
• W2024668488 cites W2040137618 @default.
• W2024668488 cites W2047945039 @default.
• W2024668488 cites W2049451196 @default.
• W2024668488 cites W2053043919 @default.
• W2024668488 cites W2060088718 @default.
• W2024668488 cites W2063733034 @default.
• W2024668488 cites W2063978545 @default.
• W2024668488 cites W2075829521 @default.
• W2024668488 cites W2076305899 @default.
• W2024668488 cites W2076733230 @default.
• W2024668488 cites W2081823884 @default.
• W2024668488 cites W2086324585 @default.
• W2024668488 cites W2097094825 @default.
• W2024668488 cites W2098503611 @default.
• W2024668488 cites W2113166966 @default.
• W2024668488 cites W2113690827 @default.
• W2024668488 cites W2123000765 @default.
• W2024668488 cites W2124097986 @default.
• W2024668488 cites W2129422864 @default.
• W2024668488 cites W2133019124 @default.
• W2024668488 cites W2134365974 @default.
• W2024668488 cites W2138206059 @default.
• W2024668488 cites W2169152986 @default.
• W2024668488 doi "https://doi.org/10.1038/ncomms3529" @default.
• W2024668488 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3826621" @default.
• W2024668488 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/24108142" @default.
• W2024668488 hasPublicationYear "2013" @default.
• W2024668488 type Work @default.
• W2024668488 sameAs 2024668488 @default.
• W2024668488 citedByCount "46" @default.
• W2024668488 countsByYear W20246684882014 @default.
• W2024668488 countsByYear W20246684882015 @default.
• W2024668488 countsByYear W20246684882016 @default.
• W2024668488 countsByYear W20246684882017 @default.
• W2024668488 countsByYear W20246684882018 @default.
• W2024668488 countsByYear W20246684882019 @default.
• W2024668488 countsByYear W20246684882020 @default.
• W2024668488 countsByYear W20246684882021 @default.
• W2024668488 countsByYear W20246684882023 @default.
• W2024668488 crossrefType "journal-article" @default.
• W2024668488 hasAuthorship W2024668488A5010518835 @default.
• W2024668488 hasAuthorship W2024668488A5013301564 @default.
• W2024668488 hasAuthorship W2024668488A5016024085 @default.
• W2024668488 hasAuthorship W2024668488A5023317571 @default.
• W2024668488 hasAuthorship W2024668488A5029219248 @default.
• W2024668488 hasAuthorship W2024668488A5037301114 @default.
• W2024668488 hasAuthorship W2024668488A5049588162 @default.
• W2024668488 hasAuthorship W2024668488A5052948447 @default.
• W2024668488 hasAuthorship W2024668488A5056711785 @default.
• W2024668488 hasAuthorship W2024668488A5070254459 @default.
• W2024668488 hasAuthorship W2024668488A5074965642 @default.
• W2024668488 hasAuthorship W2024668488A5088700318 @default.
• W2024668488 hasBestOaLocation W20246684881 @default.
• W2024668488 hasConcept C1009742 @default.
• W2024668488 hasConcept C126322002 @default.
• W2024668488 hasConcept C170493617 @default.
• W2024668488 hasConcept C181199279 @default.

• next