The beta-secretase enzyme BACE in health and Alzheimer's disease: regulation, cell biology, function, and therapeutic potential.
The beta-secretase enzyme BACE in health and Alzheimer's disease: regulation, cell biology, function, and therapeutic potential.
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DOI：
10.1523/jneurosci.3657-09.2009
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发表时间：
2009-10-14
期刊：
影响因子：
--
通讯作者：
Wong PC
中科院分区：
文献类型：
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作者：
Vassar R;Kovacs DM;Yan R;Wong PC
β - 淀粉样蛋白（Aβ）肽是阿尔茨海默病（AD）大脑中淀粉样斑块的主要成分，并且可能在这种毁灭性的神经退行性疾病的发病机制中起核心作用。β - 分泌酶，即β - 位点淀粉样前体蛋白裂解酶（BACE1；也称为Asp2，膜蛋白酶2），是负责启动Aβ产生的酶。因此，BACE是治疗性抑制AD中Aβ产生的首要药物靶点。自10年前被发现以来，人们对BACE已经有了很多了解。这篇综述总结了BACE的特性，描述了AD中BACE翻译失调，并讨论了BACE在钠电流、突触传递、髓鞘形成和精神分裂症中的生理功能。还将考虑BACE的治疗潜力。这是对神经科学学会第39届年会上举行的一次研讨会所涵盖主题的总结，并非对BACE的全面综述。
The β-amyloid (Aβ) peptide is the major constituent of amyloid plaques in Alzheimer's disease (AD) brain and is likely to play a central role in the pathogenesis of this devastating neurodegenerative disorder. The β-secretase, β-site amyloid precursor protein cleaving enzyme (BACE1; also called Asp2, memapsin 2), is the enzyme responsible for initiating Aβ generation. Thus, BACE is a prime drug target for the therapeutic inhibition of Aβ production in AD. Since its discovery 10 years ago, much has been learned about BACE. This review summarizes BACE properties, describes BACE translation dysregulation in AD, and discusses BACE physiological functions in sodium current, synaptic transmission, myelination, and schizophrenia. The therapeutic potential of BACE will also be considered. This is a summary of topics covered at a symposium held at the 39th annual meeting of the Society for Neuroscience and is not meant to be a comprehensive review of BACE.