, Volume 16, Issue 3, pp 635–648 | Cite as

Cholesterol 24-Hydroxylation by CYP46A1: Benefits of Modulation for Brain Diseases

  • Alexey M. Petrov
  • Irina A. PikulevaEmail author


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.

Key Words

CYP46A1 Cholesterol 24-Hydroxycholesterol Cholesterol turnover Efavirenz Neurodegeneration 





Acyl-coenzyme A:cholesterol acyltransferase 1


Alzheimer’s disease


Apolipoprotein A1


Cerebrospinal fluid


7-Dehydrocholesterol reductase


∆24-Dehydrocholesterol reductase


Huntington’s disease


Lecithin:cholesterol acyltransferase


Liver X receptors


Morris water maze


N-Methyl-d-aspartate receptors


Niemann-Pick C1 protein


Niemann-Pick C2 protein


Parkinson’s disease


Sterol O-acyltransferase



We thank Dr. Natalia Mast for help with the figure preparation. Some of the studies described in this review were supported in part by the National Institute of General Medical Sciences Grant GM062882 and the Alzheimer’s Drug Discovery Foundation Grant 20160601 (Irina A. Pikuleva).

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Supplementary material

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Copyright information

© The American Society for Experimental NeuroTherapeutics, Inc. 2019

Authors and Affiliations

  1. 1.Department of Ophthalmology and Visual SciencesCase Western Reserve UniversityClevelandUSA

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