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Updated: Jan 1, 2026

Focused Ultrasound Induced Blood-Brain Barrier Opening for Targeting Brain Structures and Evaluating Chemogenetic Neuromodulation
Published on: December 22, 2020
New Therapeutic Targets for Brain Function and Disease
1Department of Nuclear Medicine and Radiobiology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada.
Abstract:
Cytochrome P450 46A1 (CYP46A1) or cholesterol-24-hydroxylase is responsible for cholesterol metabolism and homeostasis in the human brain. More recently its activity has been linked to brain function and disease. The anti-HIV drug efavirenz activates CYP46A1 at low drug levels while inhibiting the enzyme activity at the high dose used in clinical practice. Synthetic analogs and hydroxylated metabolites of efavirenz enhance CYP46A1 activity, with reduced unwanted enzyme inhibition at higher concentrations. These observations provide a platform for structural modifications of efavirenz to modulate CYP46A1 activity as a therapeutic target of brain disorders such as Alzheimer's disease, for which currently no treatment is available.
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