title: Identification and biology of β-secretase.
abstract: Our knowledge of the etiology of Alzheimer's disease (AD) has advanced tremendously since the discovery of amyloid beta (Aβ) aggregation in diseased brains. Accumulating evidence suggests that Aβ plays a causative role in AD. The β-secretase enzyme, beta-site APP cleaving enzyme-1 (BACE1), is also implicated in AD pathogenesis, given that BACE1 cleavage of amyloid precursor protein is the initiating step in the formation of Aβ. As a result, BACE1 inhibition has been branded as a potential AD therapy. In this study, we review the identification and basic characteristics of BACE1, as well as the progress in our understanding of BACE1 cell biology, substrates, and phenotypes of BACE1 knockout mice that are informative about the physiological functions of BACE1 beyond amyloid precursor protein cleavage. These data are crucial for predicting potential mechanism-based toxicity that would arise from inhibiting BACE1 for the treatment or prevention of AD.
authors: Northwestern University, Feinberg School of Medicine, Department of Cell and Molecular Biology, Chicago, Illinois, USA.
authors: Patty C
authors: PC
authors: Kandalepas
authors: Northwestern University, Feinberg School of Medicine, Department of Cell and Molecular Biology, Chicago, Illinois, USA.
authors: Robert
authors: R
authors: Vassar
mesh_terms: D000544:Alzheimer Disease / Q000201:enzymology* / Q000209:etiology* / Q000378:metabolism; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000502:physiology*; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D013379:Substrate Specificity
chemical_list: D016564:Amyloid beta-Protein Precursor; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human