Gamma-secretase: a catalyst of Alzheimer disease and signal transduction.
Gamma-secretase is a membrane-bound protease that cleaves within the transmembrane region of the amyloid precursor protein to generate the C termini of both major peptides that constitute the amyloid plaques found in Alzheimer disease (AD). Recent biochemical studies provide compelling evidence that presenilins, membrane-spanning proteins associated with early-onset familial AD, are novel aspartyl proteased that function within a macromolecular complex to mediate gamma-secretase activity. These new insights underscore the role of the presenilins in regulated intramembrane proteolysis and could possibly lead to the inhibition of gamma-secretase activity as a therapy for AD.
Department of Biological Chemistry, Merck Research Laboratories, West Point, PA 19486, USA. yueming_li@merck.com
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D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism*; D053829:Amyloid Precursor Protein Secretases; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D016282:Aspartic Acid Endopeptidases; D001665:Binding Sites; D002219:Carbamates / Q000627:therapeutic use; D002384:Catalysis; D004151:Dipeptides / Q000627:therapeutic use; D010450:Endopeptidases / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D008954:Models, Biological; D015394:Molecular Structure; D058225:Plaque, Amyloid / Q000187:drug effects / Q000378:metabolism; D051880:Receptors, Notch; D015398:Signal Transduction; D013379:Substrate Specificity
C489697:APLP1 protein, human; D016564:Amyloid beta-Protein Precursor; D002219:Carbamates; D004151:Dipeptides; D004791:Enzyme Inhibitors; C410009:L 685458; D008565:Membrane Proteins; D051880:Receptors, Notch; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human