Identification of the role of presenilins beyond Alzheimer's disease.
Mutations in the genes encoding presenilin 1 (PS1) and presenilin 2 (PS2) account for the majority of the cases of familial early-onset Alzheimer's disease (FAD). Presenilins (PSs) facilitate the intramembraneous cleavage of amyloid precursor protein (APP), coined gamma-secretase cleavage, which generates beta-amyloid peptides (A beta). Considerable evidence suggests that FAD-linked PS variants exert their pathogenic influence by selectively elevating the levels of highly fibrillogenic A beta 42 peptides. In addition, numerous other functions have been ascribed to PSs based on subcellular localization, protein interactions, loss of function studies, and intramembraneous gamma-secretase cleavage of growing number of substrates. This review summarizes the diverse physiological functions that are regulated by PSs beyond APP metabolism.
Departments of Neurobiology, Pharmacology and Physiology, University of Chicago, Knapp R212, 924 East 57th Street, Chicago, IL 60637, USA. gopal@uchicago.edu
Gopal
G
Thinakaran
Angèle T
AT
Parent
D000544:Alzheimer Disease / Q000209:etiology* / Q000378:metabolism; D053829:Amyloid Precursor Protein Secretases; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D016282:Aspartic Acid Endopeptidases; D010450:Endopeptidases / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D009154:Mutation; D010446:Peptide Fragments / Q000378:metabolism; D053764:Presenilin-1
D016229:Amyloid beta-Peptides; D008565:Membrane Proteins; C508853:PSEN1 protein, human; D010446:Peptide Fragments; D053764:Presenilin-1; C075222:amyloid beta-protein (1-42); D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human