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Titolo:
The beta-secretase, BACE - A prime drug target for Alzheimer's disease
Autore:
Vassar, R;
Indirizzi:
Northwestern Univ, Sch Med, Dept Cell & Mol Biol, Chicago, IL 60611 USA Northwestern Univ Chicago IL USA 60611 & Mol Biol, Chicago, IL 60611 USA
Titolo Testata:
JOURNAL OF MOLECULAR NEUROSCIENCE
fascicolo: 2, volume: 17, anno: 2001,
pagine: 157 - 170
SICI:
0895-8696(200110)17:2<157:TBB-AP>2.0.ZU;2-H
Fonte:
ISI
Lingua:
ENG
Soggetto:
AMYLOID PRECURSOR PROTEIN; HUMAN BRAIN; TRANSGENIC MICE; BAFILOMYCIN A1; CLEAVAGE; PEPTIDE; INHIBITOR; GENE; SITE; PURIFICATION;
Keywords:
beta-secretase; BACE; Alzheimer's disease; A beta peptide; beta-amyloid; APP processing;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
63
Recensione:
Indirizzi per estratti:
Indirizzo: Vassar, R Northwestern Univ, Sch Med, Dept Cell & Mol Biol, 303 E Chicago Ave, Chicago, IL 60611 USA Northwestern Univ 303 E Chicago Ave Chicago IL USA 60611 611 USA
Citazione:
R. Vassar, "The beta-secretase, BACE - A prime drug target for Alzheimer's disease", J MOL NEURO, 17(2), 2001, pp. 157-170

Abstract

Evidence suggests that the beta -amyloid peptide (A beta) is central to the pathophysiology of Alzheimer's disease (AD). Amyloid plaques, primarily composed of A beta, progressively develop in the brains of AD patients, and mutations in three genes (A PP, PS1, and PS2) cause early onset familial AD(FAD) by directly increasing synthesis of the toxic, plaque-promoting AP42peptide. Given the strong association between A beta and AD, therapeutic strategies to lower the concentration of A beta in the brain should prove beneficial for the treatment of AD. One such strategy would involve inhibiting the enzymes that generate A beta. A beta is a product of catabolism of the large TypeI membrane protein, amyloid precursor protein (APP). Two proteases, called beta- and gamma -secretase, mediate the endoproteolysis of APP to liberate the A beta peptide. For over a decade, the molecular identitiesof these proteases were unknown. Recently, the gamma -secretase has been tentatively identified as the presenilin proteins, PS1 and PS2, and the identity of the beta -secretase has been shown to be the novel transmembrane aspartic protease, beta -site APP cleaving enzyme 1 (BACE1; also called Asp2 and memapsin2). BACE2, a novel protease homologous to BACE1, was also identified, and together the two enzymes define a new family of transmembrane aspartic proteases. BACE1 exhibits all the properties of the beta -secretase,and as the key rate-limiting enzyme that initiates the formation of A beta, BACE1 is an attractive drug target for AD. Here, I review the identification and initial characterization of BACE1 and BACE2, and summarize our current understanding of BACE1 post-translational processing and intracellular trafficking. In addition, I discuss recent studies of BACE1 knockout mice and the BACE1 X-ray structure, and relate implications for BACE1 drug development.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/01/20 alle ore 19:44:36