β-分泌酶抑制剂治疗阿尔茨海默病：前路漫漫。
Secretase inhibitors for the treatment of Alzheimer's disease: Long road ahead.
机构信息
Pharmaceutical Chemistry Research Laboratory, Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi, 221005, India.
Department of Surgery, Institute of Medical Sciences, Banaras Hindu University, Varanasi, 221005, India.
出版信息
Eur J Med Chem. 2018 Mar 25;148:436-452. doi: 10.1016/j.ejmech.2018.02.035. Epub 2018 Feb 15.
UNLABELLED
Alzheimer's disease (AD) is a neurodegenerative disease, characterized by progressive loss of memory which is associated with other cognitive deficits. The two protein structures in the brain i.e. neurofibrillary tangles and senile plaques are considered to hamper the normal cognitive activity of the brain. There are various therapeutic interpolations under investigation to thwart and treat AD. Secretases inhibitors are important agents that inhibit the development of senile plaques. β-secretase (BACE) inhibitors are in lime light for the drug development of AD. BACE initiates the production of Aβ, so its inhibition provides a valid target for the AD. BACE inhibitors viz. LY2811376, LY2886721, E2609 are in different phases of clinical trials. However, chemical study of MK8931 was discontinued due to lack of chances of finding a positive clinical effect.
AREAS COVERED
The review incorporates exhaustive literature reports on secretase inhibitors, γ-secretase modulators (GSMs) and α-secretase enhancers. The recent studies on the natural products as GSMs have also been included.
非专利药物说明
阿尔茨海默病（AD）是一种神经退行性疾病，其特征是记忆逐渐丧失，这与其他认知缺陷有关。大脑中的两种蛋白质结构，即神经纤维缠结和老年斑，被认为会阻碍大脑的正常认知活动。目前正在研究各种治疗干预措施来阻止和治疗 AD。 蛋白酶体抑制剂是抑制老年斑形成的重要药物。β-分泌酶（BACE）抑制剂是 AD 药物开发的研究热点。BACE 启动了 Aβ的产生，因此抑制 BACE 为 AD 提供了一个有效的靶点。BACE 抑制剂，如 LY2811376、LY2886721、E2609，目前处于不同的临床试验阶段。然而，由于缺乏发现积极临床效果的机会，MK8931 的化学研究已被停止。
涵盖领域
本综述综合了关于蛋白酶体抑制剂、γ-分泌酶调节剂（GSMs）和 α-分泌酶增强剂的详尽文献报告。还包括了关于天然产物作为 GSMs 的最新研究。
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