title: The proteins BACE1 and BACE2 and beta-secretase activity in normal and Alzheimer's disease brain.
abstract: The insidious progression of AD (Alzheimer's disease) is believed to be linked closely to the production, accumulation and aggregation of the approximately 4.5 kDa protein fragment called Abeta (amyloid beta-peptide). Abeta is produced by sequential cleavage of the amyloid precursor protein by two enzymes referred to as beta- and gamma-secretase. beta-Secretase is of central importance, as it catalyses the rate-limiting step in the production of Abeta and was identified 7 years ago as BACE1 (beta-site APP-cleaving enzyme 1). Soon afterwards, its homologue BACE2 was discovered, and both proteins represent a new subclass of the aspartyl protease family. Studies examining the regulation and function of beta-secretase in the normal and AD brain are central to the understanding of excessive production of Abeta in AD, and in targeting and normalizing this beta-secretase process if it has gone awry in the disease. Several reports indicate this, showing increased beta-secretase activity in AD, with recent findings by our group showing changes in beta-secretase enzyme kinetics in AD brain caused by an increased V(max). This article gives a brief review of studies which have examined BACE1 protein levels and beta-secretase activity in control and AD brain, considering further the expression of BACE2 in the human brain.
authors.affiliation: Department of Biochemistry, BioSciences Institute, University College Cork, Cork, Ireland.
authors.forename: J H
authors.initials: JH
authors.lastname: Stockley
authors.forename: C
authors.initials: C
authors.lastname: O'Neill
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016282:Aspartic Acid Endopeptidases / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D001921:Brain / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D012333:RNA, Messenger; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509284:BACE2 protein, human; C509280:BACE1 protein, human