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Author Wolfe, Michael S.
Source SpringerLink
Content type Text
Publisher Springer-Verlag
File Format PDF
Copyright Year ©2008
Language English
Subject Domain (in DDC) Technology ♦ Medicine & health
Subject Keyword Alzheimer’s disease ♦ amyloid β-protein ♦ amyloid precursor protein ♦ Notch receptor ♦ secretase ♦ γ-secretase ♦ Neurosciences ♦ Neurology ♦ Neurosurgery ♦ Neurobiology
Abstract The 4-kDa amyloid β-peptide (Aβ) is strongly implicated the pathogenesis of Alzheimer’s disease (AD), and this peptide is cut out of the amyloid β-protein precursor (APP) by the sequential action of β- and γ-secretases. γ-Secretase is a membrane-embedded protease complex that cleaves the transmembrane region of APP to produce Aβ, and this protease is a top target for developing AD therapeutics. A number of inhibitors of the γ-secretase complex have been identified, including peptidomimetics that block the active site, helical peptides that interact with the initial substrate docking site, and other less peptide-like, more drug-like compounds. To date, one γ-secretase inhibitor has advanced into late-phase clinical trials for the treatment of AD, but serious concerns remain. The γ-secretase complex cleaves a number of other substrates, and γ-secretase inhibitors cause in vivo toxicities by blocking proteolysis of one essential substrate, the Notch receptor. Thus, compounds that modulate γ-secretase, rather than inhibit it, to selectively alter Aβ production without hindering signal transduction from the Notch receptor would be more ideal. Such modulators have been discovered and advanced, with one compound in late-phase clinical trials, renewing interest in γ-secretase as a therapeutic target.
ISSN 19337213
Age Range 18 to 22 years ♦ above 22 year
Educational Use Research
Education Level UG and PG
Learning Resource Type Article
Publisher Date 2008-01-01
Publisher Institution American Society for Experimental NeuroTherapeutics
Publisher Place New York
e-ISSN 18787479
Journal NeuroRX
Volume Number 5
Issue Number 3
Page Count 8
Starting Page 391
Ending Page 398

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Source: SpringerLink