{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Toyn JH"],"funding":["NCATS NIH HHS"],"pagination":["125-37"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4931879"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["358(1)"],"pubmed_abstract":["The amyloid-β peptide (Aβ)-in particular, the 42-amino acid form, Aβ1-42-is thought to play a key role in the pathogenesis of Alzheimer's disease (AD). Thus, several therapeutic modalities aiming to inhibit Aβ synthesis or increase the clearance of Aβ have entered clinical trials, including γ-secretase inhibitors, anti-Aβ antibodies, and amyloid-β precursor protein cleaving enzyme inhibitors. A unique class of small molecules, γ-secretase modulators (GSMs), selectively reduce Aβ1-42 production, and may also decrease Aβ1-40 while simultaneously increasing one or more shorter Aβ peptides, such as Aβ1-38 and Aβ1-37. GSMs are particularly attractive because they do not alter the total amount of Aβ peptides produced by γ-secretase activity; they spare the processing of other γ-secretase substra"],"journal":["The Journal of pharmacology and experimental therapeutics"],"pubmed_title":["Robust Translation of γ-Secretase Modulator Pharmacology across Preclinical Species and Human Subjects."],"pmcid":["PMC4931879"],"funding_grant_id":["UL1 TR001863"],"pubmed_authors":["Zuev D","Clarke W","Gasior M","Padmanabha R","Berisha F","Furlong M","Raybon J","Olson RE","Drexler DM","Zhuo X","Boy KM","Lentz KA","Wang JS","Wei C","Denton RR","Guss V","Snow K","Grace J","Sweeney F","Ahlijanian MK","Robertson AS","Morrison J","Cook L","Hoque N","AbuTarif M","Thompson LA","Meredith JE","Soares HD","Albright CF","Hong Q","Toyn JH","Macor JE"],"additional_accession":[]},"is_claimable":false,"name":"Robust Translation of γ-Secretase Modulator Pharmacology across Preclinical Species and Human Subjects.","description":"The amyloid-β peptide (Aβ)-in particular, the 42-amino acid form, Aβ1-42-is thought to play a key role in the pathogenesis of Alzheimer's disease (AD). Thus, several therapeutic modalities aiming to inhibit Aβ synthesis or increase the clearance of Aβ have entered clinical trials, including γ-secretase inhibitors, anti-Aβ antibodies, and amyloid-β precursor protein cleaving enzyme inhibitors. A unique class of small molecules, γ-secretase modulators (GSMs), selectively reduce Aβ1-42 production, and may also decrease Aβ1-40 while simultaneously increasing one or more shorter Aβ peptides, such as Aβ1-38 and Aβ1-37. GSMs are particularly attractive because they do not alter the total amount of Aβ peptides produced by γ-secretase activity; they spare the processing of other γ-secretase substra","dates":{"release":"2016-01-01T00:00:00Z","publication":"2016 Jul","modification":"2026-05-05T15:05:50.762Z","creation":"2019-03-27T02:17:31Z"},"accession":"S-EPMC4931879","cross_references":{"pubmed":["27189974"],"doi":["10.1124/jpet.116.232249"]}}