Efavirenz As A Potential Anti-Alzheimers Disease Medication | 101407
Journal of Traditional Medicine & Clinical Naturopathy
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Efavirenz is the anti-HIV medication given daily at a 600 mg dose to keep the viral
load low. We found that in mice, a very low dose of efavirenz (100-times lower than
that given to HIV patients) enhances the activity of the brain enzyme cytochrome P450
46A1 (CYP46A1), which converts cholesterol to 24-hydroxycholesterol. Cholesterol
24-hydroxylation is the major pathway of cholesterol elimination from the brain;
CYP46A1 controls this pathway and thereby cholesterol turnover in the brain. 5XFAD
mice, a model of rapid amyloidogenesis, were treated daily with a 0.1 mg/kg of body
weight efavirenz dose, which was delivered in drinking water. The treatment started at one
month of age and continued for eight months. Efavirenz administration stably activated
CYP46A1 and enhanced cholesterol turnover in the 5XFAD brain. 5XFAD mice also had
a significant reduction in amyloid-b burden and microglia activation in the brain cortex
and hippocampus. Mouse performance was improved in Morris water maze test, and the
treated animals had a significant reduction in mortality rates. The data obtained suggest
that efavirenz should be considered as an anti-Alzheimer's disease medication, and the
pathway of the brain cholesterol removal as a therapeutic target for this disease. A clinical
trial is in progress to evaluate efavirenz effects on people with mild cognitive impairment
due to Alzheimer's disease.
Irina A Pikuleva has completed her PhD in Biochemistry from the Buelorussian Academy of Sciences and completed her Post-doctoral studies at Vanderbilt University. Currently, she is the Vice Chair for Research of the Department of Ophthalmology and Visual Sciences and Director of the Visual Sciences Research Center at Case Western Reserve University. She has published more than 100 peer-reviewed papers and has served as a Reviewer on the study sections of the National Institutes of Healths as well as private foundations.