CYP46A1 Activation by Efavirenz Leads to Behavioral Improvement without Significant Changes in Amyloid Plaque Load in the Brain of 5XFAD Mice.

ABSTRACT: Efavirenz, the FDA-approved anti-retroviral medication, is evaluated in the clinical trial in patients with mild cognitive impairment or early dementia due to Alzheimer's disease. Efavirenz is assessed for activation of cytochrome P450 46A1 (CYP46A1), a CNS-specific enzyme that converts cholesterol to 24-hydroxycholesterol. Cholesterol 24-hydroxylation is the major pathway for brain cholesterol removal, and a mechanism that controls brain cholesterol turnover. The present study tested efavirenz on 5XFAD mice (an Alzheimer's model) at a very low daily dose of 0.1 mg/kg body weight. Efavirenz treatment started from three months of age, after amyloid plague appearance, and continued for 6 months. This treatment led to CYP46A1 activation in the brain, enhancement of brain cholesterol turnover,

SUBMITTER: Petrov AM 

PROVIDER: S-EPMC6694340 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature