The Normal and Pathologic Roles of the Alzheimer's β-secretase, BACE1

被引：47

作者：

Kandalepas, Patty C. ^{[1
]}

Vassar, Robert ^{[1
]}

机构：

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

来源：

CURRENT ALZHEIMER RESEARCH | 2014年 / 11卷 / 05期

关键词：

Alzheimer's disease; BACE1; beta-secretase; AMYLOID PRECURSOR PROTEIN; GATED SODIUM-CHANNELS; OLFACTORY SENSORY NEURONS; A-BETA; CELL-ADHESION; CLEAVING ENZYME; TRANSGENIC MICE; ASPARTYL PROTEASE; MEMORY DEFICITS; GENE-EXPRESSION;

D O I：

10.2174/1567205011666140604122059

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

As the most common neurodegenerative disease, therapeutic avenues for the treatment and prevention of Alzheimer's Disease are highly sought after. The aspartic protease BACE1 is the initiator enzyme for the formation of A beta, a major constituent of amyloid plaques that represent one of the hallmark pathological features of this disorder. Thus, targeting BACE1 for disease-modifying AD therapies represents a rationale approach. The collective knowledge acquired from investigations of BACE1 deletion mutants and characterization of BACE1 substrates has downstream significance not only for the discovery of AD drug therapies but also for predicting side effects of BACE1 inhibition. Here we discuss the identification and validation of BACE1 as the beta-secretase implicated in AD, in addition to information regarding BACE1 cell biology, localization, substrates and potential physiological functions derived from BACE1 knockout models.

引用

页码：441 / 449

页数：9

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