ArticleNeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics2019
CYP46A1 Activation by Efavirenz Leads to Behavioral Improvement without Significant Changes in Amyloid Plaque Load in the Brain of 5XFAD Mice.
Article in Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
61 citing papers in PubMed, 1 synthesis or guideline pooled it, 84 citations in OpenAlex.
- Pooled it
- CYP46A1 activation by low-dose efavirenz enhances brain cholesterol metabolism in subjects with early Alzheimer's disease.Alzheimer's research & therapy · 2022Trial
- CYP46A1-Targeted Treatment Alleviates Long-Term White Matter Injury Following Traumatic Brain Injury by Promoting Cholesterol Metabolic Clearance and Remyelination.CNS neuroscience & therapeutics · 2026Article
- CYP46A1 activation by low-dose efavirenz uncovers the link between brain cholesterol metabolism, energetics, and vasculature.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2026Article
- Gut microbiota-dependent 24-hydroxycholesterol metabolism contributes to capsaicin-induced amelioration of Alzheimer's disease-like pathology in mice.Nature communications · 2026Article
- Efavirenz treatment improves retinal vaso-obliteration and pathological neovascularization in a mouse model of retinopathy of prematurity.Frontiers in medicine · 2026Article
- Mechanisms, Mediators, and Pharmacological Approaches Targeting Brain Cholesterol Transport in Alzheimer's Disease.Current pharmaceutical design · 2026Review
- Frequency-Dependent Mechanism of 24-Hydroxycholesterol-Mediated Modulation of Neurotransmitter Release at the Mouse Neuromuscular Junction: The Role of Reactive Oxygen Species.Neurochemical research · 2025Article
- Cholesterol-Lowering Treatment Suppresses Neuromuscular Transmission Via Presynaptic Mechanism at the Mouse Diaphragm Muscle.Neurochemical research · 2025Article
- Sterol imbalances and cholesterol-24-hydroxylase dysregulation is linked to the underlying progression of multiple sclerosis.Brain pathology (Zurich, Switzerland) · 2025Article
- Cholesterol-modifying strategies for Alzheimer disease: promise or fallacy?Expert review of neurotherapeutics · 2025Review
- Brain Cytochrome P450: Navigating Neurological Health and Metabolic Regulation.Journal of xenobiotics · 2025Review
- Challenges and Opportunities for Consideration of Efavirenz Drug Repurposing for Alzheimer's Disease Therapeutics.ACS pharmacology & translational science · 2024Review
- Calycosin-7-O-β-D-Glucoside Ameliorates Palmitate-Induced Lipid Accumulation in HT22 Cells.Actas espanolas de psiquiatria · 2024Article
- DHM/SERS reveals cellular morphology and molecular changes during iPSCs-derived activation of astrocytes.Biomedical optics express · 2024Article
- Rescuing tri-heteromeric NMDA receptor function: the potential of pregnenolone-sulfate in loss-of-function GRIN2B variants.Cellular and molecular life sciences : CMLS · 2024Article
- Brain cholesterol and Alzheimer's disease: challenges and opportunities in probe and drug development.Brain : a journal of neurology · 2024Review
- Navigating the metabolic maze: anomalies in fatty acid and cholesterol processes in Alzheimer's astrocytes.Alzheimer's research & therapy · 2024Review
- Effects of Complete and Partial Loss of the 24S-Hydroxycholesterol-Generating EnzymeBiomolecules · 2024Article
- 7,8-Dihydroxy Efavirenz Is Not as Effective in CYP46A1 Activation In Vivo as Efavirenz or Its 8,14-Dihydroxy Metabolite.International journal of molecular sciences · 2024Article
1 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
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, behavioral improvements, reduction in microglia activation but increased astrocyte reactivity. The levels of the soluble and insoluble amyloid 40 and 42 peptides were unchanged while the number and area of the dense core amyloid plaques were slightly decreased. The measurements of the brain levels of several pre- and post-synaptic proteins (Munc13-1, PSD-95, gephyrin, synaptophysin, synapsin-1, and calbindin-D28k) suggested efavirenz effect at the synaptic level. Efavirenz treatment in the present work seems to represent a model of behavioral and other improvements independent of the levels of the amyloid peptides and provides insight into potential outcomes of the future clinical trial.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.