ArticlePloS one2017
Transcriptional and post-translational changes in the brain of mice deficient in cholesterol removal mediated by cytochrome P450 46A1 (CYP46A1).
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 31 citations in OpenAlex.
- CYP46A1 activation by low-dose efavirenz uncovers the link between brain cholesterol metabolism, energetics, and vasculature.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2026Article
- Effects of Complete and Partial Loss of the 24S-Hydroxycholesterol-Generating EnzymeBiomolecules · 2024Article
- The translational potential of cholesterol-based therapies for neurological disease.Nature reviews. Neurology · 2023Review
- Tissue-Specific Oxysterols as Predictors of Antidepressant (Escitalopram) Treatment Response in Patients With Major Depressive Disorder.Biological psychiatry global open science · 2023Article
- Investigation of Potential Drug Targets for Cholesterol Regulation to Treat Alzheimer's Disease.International journal of environmental research and public health · 2023Article
- 24-Hydroxycholesterol Moderates the Effects of Amyloid-β on Expression of HMG-CoA Reductase and ABCA1 Proteins in Mouse Astrocytes.Advanced biomedical research · 2023Article
- Lipolysis-Stimulated Lipoprotein Receptor Acts as Sensor to Regulate ApoE Release in Astrocytes.International journal of molecular sciences · 2022Article
- Altered Cholesterol Homeostasis in Huntington's Disease.Frontiers in aging neuroscience · 2022Review
- Targeting cytochrome P450 46A1 and brain cholesterol 24-hydroxylation to treat neurodegenerative diseases.Exploration of neuroprotective therapy · 2021Article
- Cholesterol Hydroxylating Cytochrome P450 46A1: From Mechanisms of Action to Clinical Applications.Frontiers in aging neuroscience · 2021Review
- Localization of sterols and oxysterols in mouse brain reveals distinct spatial cholesterol metabolism.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Brain sterol flux mediated by cytochrome P450 46A1 affects membrane properties and membrane-dependent processes.Brain communications · 2020Article
- Effects of CYP46A1 Inhibition on Long-Term-Depression in Hippocampal SlicesFrontiers in molecular neuroscience · 2020Article
- Cholesterol Biosynthesis and Uptake in Developing Neurons.ACS chemical neuroscience · 2019Article
- The key genes, phosphoproteins, processes, and pathways affected by efavirenz-activated CYP46A1 in the amyloid-decreasing paradigm of efavirenz treatment.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Cholesterol 24-Hydroxylation by CYP46A1: Benefits of Modulation for Brain Diseases.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2019Review
- Preferential enhancement of GluN2B-containing native NMDA receptors by the endogenous modulator 24S-hydroxycholesterol in hippocampal neurons.Neuropharmacology · 2019Article
- Brain cholesterol metabolism and Parkinson's disease.Movement disorders : official journal of the Movement Disorder Society · 2019Article
- Retinal Vascular Abnormalities and Microglia Activation in Mice with Deficiency in Cytochrome P450 46A1-Mediated Cholesterol Removal.The American journal of pathology · 2019Article
- Article
Corrections and comments
- Erratum issued
Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Cytochrome P450 46A1 (CYP46A1) converts cholesterol to 24-hydroxycholesterol and thereby controls the major pathways of cholesterol removal from the brain. Cyp46a1-/- mice have a reduction in the rate of cholesterol biosynthesis in the brain and significant impairments to memory and learning. To gain insights into the mechanisms underlying Cyp46a1-/- phenotype, we used Cyp46a1-/- mice and quantified their brain sterol levels and the expression of the genes pertinent to cholesterol homeostasis. We also compared the Cyp46a1-/- and wild type brains for protein phosphorylation and ubiquitination. The data obtained enable the following inferences. First, there seems to be a compensatory upregulation in the Cyp46a1-/- brain of the pathways of cholesterol storage and CYP46A1-independent removal. Second, transcriptional regulation of the brain cholesterol biosynthesis via sterol regulatory element binding transcription factors is not significantly activated in the Cyp46a1-/- brain to explain a compensatory decrease in cholesterol biosynthesis. Third, some of the liver X receptor target genes (Abca1) are paradoxically upregulated in the Cyp46a1-/- brain, possibly due to a reduced activation of the small GTPases RAB8, CDC42, and RAC as a result of a reduced phosphorylation of RAB3IP and PAK1. Fourth, the phosphorylation of many other proteins (a total of 146) is altered in the Cyp46a1-/- brain, including microtubule associated and neurofilament proteins (the MAP and NEF families) along with proteins related to synaptic vesicles and synaptic neurotransmission (e.g., SLCs, SHANKs, and BSN). Fifth, the extent of protein ubiquitination is increased in the Cyp46a1-/- brain, and the affected proteins pertain to ubiquitination (UBE2N), cognition (STX1B and ATP1A2), cytoskeleton function (TUBA1A and YWHAZ), and energy production (ATP1A2 and ALDOA). The present study demonstrates the diverse potential effects of CYP46A1 deficiency on brain functions and identifies important proteins that could be affected by this deficiency.
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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.