ArticleNeuropharmacology2017
Cholesterol-metabolizing enzyme cytochrome P450 46A1 as a pharmacologic target for Alzheimer's disease.
Article in Neuropharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03706885 (A Proof-of-Concept Clinical Research Study of Efavirenz in Patients With Alzheimer's Disease), which is not on this map. Cited by 67 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
A Proof-of-Concept Clinical Research Study of Efavirenz in Patients With Alzheimer's Disease
Who cites it
67 citing papers in PubMed, 102 citations in OpenAlex.
- CYP46A1 activation by low-dose efavirenz enhances brain cholesterol metabolism in subjects with early Alzheimer's disease.Alzheimer's research & therapy · 2022Trial
- Cholesterol at the Center of Alzheimer's Disease: A Unifying Hypothesis on the Pathogenic Mechanism.Molecules (Basel, Switzerland) · 2026Review
- Recent advances in Alzheimer's disease: From molecular mechanisms to therapeutic strategies.Cell · 2026Review
- 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
- Cholesterol metabolism in neurodegenerative diseases: mechanisms and therapeutic advances.Molecular neurodegeneration · 2026Review
- Gut microbiota-dependent 24-hydroxycholesterol metabolism contributes to capsaicin-induced amelioration of Alzheimer's disease-like pathology in mice.Nature communications · 2026Article
- Metabolic alteration in oxylipins and endocannabinoids point to an important role for soluble epoxide hydrolase and inflammation in Alzheimer's disease-finding from Alzheimer's Disease Neuroimaging Initiative.Alzheimer's research & therapy · 2026Article
- Cholesterol metabolic reprogramming mediates microglia-induced chronic neuroinflammation and hinders neurorestoration following stroke.Nature metabolism · 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
- Disrupted calcium dynamics and electrophysiological activity in the stratum pyramidale and hippocampal alveus during fear conditioning in the 5xFAD model of Alzheimer's disease.Frontiers in aging neuroscience · 2025Article
- The Neural Palette of Heme: Altered Heme Homeostasis Underlies Defective Neurotransmission, Increased Oxidative Stress, and Disease Pathogenesis.Antioxidants (Basel, Switzerland) · 2024Review
- Challenges and Opportunities for Consideration of Efavirenz Drug Repurposing for Alzheimer's Disease Therapeutics.ACS pharmacology & translational science · 2024Review
- Brain cholesterol and Alzheimer's disease: challenges and opportunities in probe and drug development.Brain : a journal of neurology · 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
- Gut microbiota metabolites: potential therapeutic targets for Alzheimer's disease?Frontiers in pharmacology · 2024Review
- Oxysterols as Biomarkers of Aging and Disease.Advances in experimental medicine and biology · 2024Article
- Reexamining the Causes and Effects of Cholesterol Deposition in the Brains of Patients with Alzheimer's Disease.Molecular neurobiology · 2023Review
7 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Cytochrome P450 46A1 (CYP46A1 or cholesterol 24-hydroxylase) controls cholesterol elimination from the brain and plays a role in higher order brain functions. Genetically enhanced CYP46A1 expression in mouse models of Alzheimer's disease mitigates the manifestations of this disease. We enhanced CYP46A1 activity pharmacologically by treating 5XFAD mice, a model of rapid amyloidogenesis, with a low dose of the anti-HIV medication efavirenz. Efavirenz was administered from 1 to 9 months of age, and mice were evaluated at specific time points. At one month of age, cholesterol homeostasis was already disturbed in the brain of 5XFAD mice. Nevertheless, efavirenz activated CYP46A1 and mouse cerebral cholesterol turnover during the first four months of administration. This treatment time also reduced amyloid burden and microglia activation in the cortex and subiculum of 5XFAD mice as well as protein levels of amyloid precursor protein and the expression of several genes involved in inflammatory response. However, mouse short-term memory and long-term spatial memory were impaired, whereas learning in the context-dependent fear test was improved. Additional four months of drug administration (a total of eight months of treatment) improved long-term spatial memory in the treated as compared to the untreated mice, further decreased amyloid-β content in 5XFAD brain, and also decreased the mortality rate among male mice. We propose a mechanistic model unifying the observed efavirenz effects. We suggest that CYP46A1 activation by efavirenz could be a new anti-Alzheimer's disease treatment and a tool to study and identify normal and pathological brain processes affected by cholesterol maintenance.
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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 Socratic graph.