FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2093993008> ?p ?o ?g. }

• W2093993008 abstract "Alzheimer's disease (AD) is the most prevalent form of dementia in the elderly and currently only symptomatic treatments are available. The underlying biochemistry of the disease appears to involve accumulation of the toxic amyloid-β peptide (Aβ) in the brain. Aβ is formed through proteolytic cleavage of the amyloid precursor protein (APP) by the proteases BACE and γ-secretase making development of inhibitors to both enzymes attractive therapeutic approaches for Alzheimer's disease. In addition to APP, γ-secretase cleaves other proteins thereby complicating the development of γ-secretase inhibitors. Of particular concern are the Notch-family of proteins which require γ-secretase cleavage to control cell fate decisions in several tissues, including the gastrointestinal tract and spleen. Here we describe γ-secretase inhibitors possessing intrinsically different inhibitory potencies for Aβ production and Notch signaling, observing a 500-fold range in the Notch/Aβ IC50 ratios among the set of inhibitors studied. To explore the biological relevance of these findings, a cellular model for differentiation of intestinal goblet cells was developed using the HT29 colon cancer cell line. Using this assay, we found that induction of goblet cell-like differentiation could be induced by γ-secretase inhibitors at potencies similar to those measured for inhibition of Notch signaling and that Notch signaling was required for this induction. Taken together, these findings demonstrate that inhibition of Aβ formation and Notch signaling can be partially separated in cultured cells and raise the possibility that Aβ can be inhibited without Notch toxicity in vivo leading to an increased therapeutic index with select γ-secretase inhibitors." @default.
• W2093993008 created "2016-06-24" @default.
• W2093993008 creator A5015133572 @default.
• W2093993008 creator A5019656644 @default.
• W2093993008 creator A5034097461 @default.
• W2093993008 creator A5041844532 @default.
• W2093993008 creator A5046225712 @default.
• W2093993008 creator A5046585950 @default.
• W2093993008 creator A5051068757 @default.
• W2093993008 creator A5051473108 @default.
• W2093993008 creator A5056136281 @default.
• W2093993008 creator A5060331261 @default.
• W2093993008 creator A5063170079 @default.
• W2093993008 creator A5066992840 @default.
• W2093993008 creator A5068989165 @default.
• W2093993008 creator A5070894857 @default.
• W2093993008 creator A5074354123 @default.
• W2093993008 creator A5075362425 @default.
• W2093993008 creator A5076140444 @default.
• W2093993008 creator A5081370900 @default.
• W2093993008 creator A5081552804 @default.
• W2093993008 creator A5089121353 @default.
• W2093993008 date "2010-07-01" @default.
• W2093993008 modified "2023-09-27" @default.
• W2093993008 title "P3-288: Gamma-secretase inhibitors have intrinsically different potencies against Aβ production and Notch signaling" @default.
• W2093993008 doi "https://doi.org/10.1016/j.jalz.2010.05.1788" @default.
• W2093993008 hasPublicationYear "2010" @default.
• W2093993008 type Work @default.
• W2093993008 sameAs 2093993008 @default.
• W2093993008 citedByCount "0" @default.
• W2093993008 crossrefType "journal-article" @default.
• W2093993008 hasAuthorship W2093993008A5015133572 @default.
• W2093993008 hasAuthorship W2093993008A5019656644 @default.
• W2093993008 hasAuthorship W2093993008A5034097461 @default.
• W2093993008 hasAuthorship W2093993008A5041844532 @default.
• W2093993008 hasAuthorship W2093993008A5046225712 @default.
• W2093993008 hasAuthorship W2093993008A5046585950 @default.
• W2093993008 hasAuthorship W2093993008A5051068757 @default.
• W2093993008 hasAuthorship W2093993008A5051473108 @default.
• W2093993008 hasAuthorship W2093993008A5056136281 @default.
• W2093993008 hasAuthorship W2093993008A5060331261 @default.
• W2093993008 hasAuthorship W2093993008A5063170079 @default.
• W2093993008 hasAuthorship W2093993008A5066992840 @default.
• W2093993008 hasAuthorship W2093993008A5068989165 @default.
• W2093993008 hasAuthorship W2093993008A5070894857 @default.
• W2093993008 hasAuthorship W2093993008A5074354123 @default.
• W2093993008 hasAuthorship W2093993008A5075362425 @default.
• W2093993008 hasAuthorship W2093993008A5076140444 @default.
• W2093993008 hasAuthorship W2093993008A5081370900 @default.
• W2093993008 hasAuthorship W2093993008A5081552804 @default.
• W2093993008 hasAuthorship W2093993008A5089121353 @default.
• W2093993008 hasBestOaLocation W20939930081 @default.
• W2093993008 hasConcept C126322002 @default.
• W2093993008 hasConcept C161879069 @default.
• W2093993008 hasConcept C175344181 @default.
• W2093993008 hasConcept C181199279 @default.
• W2093993008 hasConcept C182220744 @default.
• W2093993008 hasConcept C185592680 @default.
• W2093993008 hasConcept C202769670 @default.
• W2093993008 hasConcept C2778171954 @default.
• W2093993008 hasConcept C2779134260 @default.
• W2093993008 hasConcept C31705614 @default.
• W2093993008 hasConcept C36103677 @default.
• W2093993008 hasConcept C502032728 @default.
• W2093993008 hasConcept C502942594 @default.
• W2093993008 hasConcept C55493867 @default.
• W2093993008 hasConcept C62478195 @default.
• W2093993008 hasConcept C71924100 @default.
• W2093993008 hasConcept C86803240 @default.
• W2093993008 hasConcept C95444343 @default.
• W2093993008 hasConceptScore W2093993008C126322002 @default.
• W2093993008 hasConceptScore W2093993008C161879069 @default.
• W2093993008 hasConceptScore W2093993008C175344181 @default.
• W2093993008 hasConceptScore W2093993008C181199279 @default.
• W2093993008 hasConceptScore W2093993008C182220744 @default.
• W2093993008 hasConceptScore W2093993008C185592680 @default.
• W2093993008 hasConceptScore W2093993008C202769670 @default.
• W2093993008 hasConceptScore W2093993008C2778171954 @default.
• W2093993008 hasConceptScore W2093993008C2779134260 @default.
• W2093993008 hasConceptScore W2093993008C31705614 @default.
• W2093993008 hasConceptScore W2093993008C36103677 @default.
• W2093993008 hasConceptScore W2093993008C502032728 @default.
• W2093993008 hasConceptScore W2093993008C502942594 @default.
• W2093993008 hasConceptScore W2093993008C55493867 @default.
• W2093993008 hasConceptScore W2093993008C62478195 @default.
• W2093993008 hasConceptScore W2093993008C71924100 @default.
• W2093993008 hasConceptScore W2093993008C86803240 @default.
• W2093993008 hasConceptScore W2093993008C95444343 @default.
• W2093993008 hasIssue "4S_Part_17" @default.
• W2093993008 hasLocation W20939930081 @default.
• W2093993008 hasOpenAccess W2093993008 @default.
• W2093993008 hasPrimaryLocation W20939930081 @default.
• W2093993008 hasRelatedWork W1675105744 @default.
• W2093993008 hasRelatedWork W1991697476 @default.
• W2093993008 hasRelatedWork W2019216667 @default.
• W2093993008 hasRelatedWork W2022435711 @default.
• W2093993008 hasRelatedWork W2030657258 @default.
• W2093993008 hasRelatedWork W2038820492 @default.
• W2093993008 hasRelatedWork W2057713102 @default.
• W2093993008 hasRelatedWork W2082631056 @default.

• next