title: Post-translational regulation of the β-secretase BACE1.
abstract: β-Secretase, widely known as β-site APP cleaving enzyme 1 (BACE1), is a membrane-associated protease that cleaves amyloid precursor protein (APP) to generate amyloid β-protein (Aβ). As this cleavage is a pathologically relevant event in Alzheimer's disease, BACE1 is considered a viable therapeutic target. BACE1 can be regulated at the transcriptional, post-transcriptional, translational, and post-translational levels. Elucidation of the regulatory pathways of BACE1 is critical, not only for understanding the pathological mechanisms of AD but also developing effective therapeutic strategies to inhibit activity of the protease. This mini-review focuses on the post-translational regulation of BACE1, as modulation at this level is closely associated with both physiological and pathological conditions. Current knowledge on the mechanisms underlying such BACE1 regulation and their implications for therapy are discussed.
authors.affiliation: Department of Demyelinating Disease and Aging, National Institute of Neuroscience, NCNP, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8502, Japan. Electronic address: araki@ncnp.go.jp.
authors.forename: Wataru
authors.initials: W
authors.lastname: Araki
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism*; D000818:Animals; D005786:Gene Expression Regulation; D006801:Humans; D011499:Protein Processing, Post-Translational
chemical_list: D053829:Amyloid Precursor Protein Secretases
keywords: Alzheimer’s disease; Amyloid β-protein; BACE1; Oligomer; Trafficking; β-Secretase