期刊
NEUROTHERAPEUTICS
卷 16, 期 3, 页码 635-648出版社
SPRINGER
DOI: 10.1007/s13311-019-00731-6
关键词
Cholesterol; 24-Hydroxycholesterol; Cholesterol turnover; Efavirenz; Neurodegeneration
资金
- National Institute of General Medical Sciences [GM062882]
- Alzheimer's Drug Discovery Foundation [20160601]
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.
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