Targeting the β secretase BACE1 for Alzheimer's disease therapy

被引：524

作者：

Yan, Riqiang ^{[1
]}

Vassar, Robert ^{[2
]}

机构：

[1] Cleveland Clin, Lerner Res Inst, Cleveland, OH 44106 USA

[2] Northwestern Univ, Dept Cell & Mol Biol, Feinberg Sch Med, Chicago, IL 60611 USA

来源：

LANCET NEUROLOGY | 2014年 / 13卷 / 03期

关键词：

AMYLOID PRECURSOR PROTEIN; OLFACTORY SENSORY NEURONS; MEMORY DEFICITS; KNOCKOUT MICE; CLOSE HOMOLOG; INCREASED EXPRESSION; CLEAVING ENZYME-1; GENETIC DELETION; AXON GUIDANCE; MOUSE MODELS;

D O I：

10.1016/S1474-4422(13)70276-X

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

The beta secretase, widely known as beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), initiates the production of the toxic amyloid beta (A beta) that plays a crucial early part in Alzheimer's disease pathogenesis. BACE1 is a prime therapeutic target for lowering cerebral A beta concentrations in Alzheimer's disease, and clinical development of BACE1 inhibitors is being intensely pursued. Although BACE1 inhibitor drug development has proven challenging, several promising BACE1 inhibitors have recently entered human clinical trials. The safety and efficacy of these drugs are being tested at present in healthy individuals and patients with Alzheimer's disease, and will soon be tested in individuals with presymptomatic Alzheimer's disease. Although hopes are high that BACE1 inhibitors might be efficacious for the prevention or treatment of Alzheimer's disease, concerns have been raised about potential mechanism-based side-effects of these drugs. The potential of therapeutic BACE1 inhibition might prove to be a watershed in the treatment of Alzheimer's disease.

引用

页码：319 / 329

页数：11

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