title: BACE1 in Alzheimer's disease.
abstract: Targeting BACE1 (β-site APP cleaving enzyme 1 or β-secretase) is the focus of Alzheimer's disease (AD) research because this aspartyl protease is involved in the abnormal production of β amyloid plaques (Aβ), the hallmark of its pathophysiology. Evidence suggests that there is a strong connection between AD and BACE1. As such, strategies to inhibit Aβ formation in the brain should prove beneficial for AD treatment. Aβ, the product of the large type1 trans-membrane protein amyloid precursor protein (APP), is produced in a two-step proteolytic process initiated by BACE1 (β-secretase) and followed by γ-secretase. Due to its apparent rate limiting function, BACE1 appears to be a prime target to prevent Aβ generation in AD. Following its discovery, the BACE1 has been cloned, its structure solved, novel physiologic substrates discovered and numerous inhibitors developed. This review focuses on elucidating the role of BACE1 to facilitate drug development in the treatment of AD.
authors.affiliation: Department of Biochemistry, Bharathidasan University, Trichy 24, India.
authors.forename: M
authors.initials: M
authors.lastname: Sathya
authors.forename: P
authors.initials: P
authors.lastname: Premkumar
authors.forename: C
authors.initials: C
authors.lastname: Karthick
authors.forename: P
authors.initials: P
authors.lastname: Moorthi
authors.forename: K S
authors.initials: KS
authors.lastname: Jayachandran
authors.forename: M
authors.initials: M
authors.lastname: Anusuyadevi
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000201:enzymology* / Q000378:metabolism; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D003001:Cloning, Molecular; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D012333:RNA, Messenger; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human; C509282:Bace1 protein, mouse