Complex regulation of γ-secretase: From obligatory to modulatory subunits Journal Article


Authors: Gertsik, N.; Chiu, D.; Li, Y. M.
Article Title: Complex regulation of γ-secretase: From obligatory to modulatory subunits
Abstract: γ-Secretase is a four subunit, 19-pass transmembrane enzyme that cleaves amyloid precursor protein (APP), catalyzing the formation of amyloid beta (Aß) peptides that form amyloid plaques, which contribute to Alzheimer's disease (AD) pathogenesis. γSecretase also cleaves Notch, among many other type I transmembrane substrates. Despite its seemingly promiscuous enzymatic capacity, γsecretase activity is tightly regulated. This regulation is a function of many cellular entities, including but not limited to the essential γsecretase subunits, nonessential (modulatory) subunits, and γsecretase substrates. Regulation is also accomplished by an array of cellular events, such as presenilin (active subunit of γsecretase) endoproteolysis and hypoxia. In this review we discuss how γsecretase is regulated with the hope that an advanced understanding of these mechanisms will aid in the development of effective therapeutics for γsecretase-associated diseases like AD and Notch-addicted cancer.
Keywords: unclassified drug; review; nonhuman; neoplasm; notch receptor; enzyme regulation; membrane protein; hypoxia inducible factor 1alpha; alzheimer disease; nicastrin; presenilin; gamma secretase; notch; alzheimer's disease; hif-1α; γ-secretase; app; human; ß-amyloid; membrane protein aph1; membrane protein gsap; membrane protein pen2
Journal Title: Frontiers in Aging Neuroscience
Volume: 6
ISSN: 1663-4365
Publisher: Frontiers Research Foundation  
Date Published: 2015-01-01
Start Page: 342
Language: English
DOI: 10.3389/fnagi.2014.00342
PROVIDER: scopus
PMCID: PMC4285130
PUBMED: 25610395
DOI/URL:
Notes: Export Date: 2 March 2015 -- Source: Scopus
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MSK Authors
  1. Yueming Li
    102 Li
  2. Danica Chiu
    2 Chiu
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