CYP46A1 介导的胆固醇 24-羟化作用：调控对脑部疾病的益处。
Cholesterol 24-Hydroxylation by CYP46A1: Benefits of Modulation for Brain Diseases.
机构信息
Department of Ophthalmology and Visual Sciences, Case Western Reserve University, 2085 Adelbert Rd., Room 303, Cleveland, OH, 44106, USA.
出版信息
Neurotherapeutics. 2019 Jul;16(3):635-648. doi: 10.1007/s13311-019-00731-6.
Abstract
Cholesterol 24-hydroxylation is the major mechanism for cholesterol removal from the brain and the reaction catalyzed by cytochrome P450 46A1 (CYP46A1), a CNS-specific enzyme. This review describes CYP46A1 in the context of cholesterol homeostasis in the brain and summarizes available experimental data on CYP46A1 association with different neurologic diseases, including the mechanisms by which changes in the CYP46A1 activity in the brain could be beneficial for these diseases. The modulation of CYP46A1 activity by genetic and pharmacologic means is also presented along with a brief synopsis of the two clinical trials that evaluate CYP46A1 as a therapeutic target for Alzheimer's disease as well as Dravet and Lennox-Gastaut syndromes.
摘要
胆固醇 24-羟化作用是大脑中胆固醇清除的主要机制，该反应由细胞色素 P450 46A1（CYP46A1）催化，CYP46A1 是一种中枢神经系统特异性酶。本综述描述了 CYP46A1 在大脑中胆固醇稳态中的作用，并总结了关于 CYP46A1 与不同神经疾病之间关联的现有实验数据，包括 CYP46A1 活性变化对这些疾病可能有益的机制。本文还介绍了通过遗传和药理学手段调节 CYP46A1 活性的情况，并简要概述了两项临床试验，这两项临床试验评估了 CYP46A1 作为阿尔茨海默病以及 Dravet 和 Lennox-Gastaut 综合征的治疗靶点的潜力。
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