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Cytochrome P450, family 46, subfamily A, polypeptide 1

CYP46A1, CYP46, cholesterol 24-hydroxylase, CP-46
This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This endoplasmic reticulum protein is expressed in the brain, where it converts cholesterol to 24S-hydroxycholesterol. While cholesterol cannot pass the blood-brain barrier, 24S-hydroxycholesterol can be secreted in the brain into the circulation to be returned to the liver for catabolism. [provided by RefSeq, Jul 2008] (from NCBI)
Top mentioned proteins: apolipoprotein E, AGE, HAD, CAN, V1a
Papers on CYP46A1
Endogenous 24S-hydroxycholesterol modulates NMDAR-mediated function in hippocampal slices.
Mennerick et al., Washington, D.C., United States. In J Neurophysiol, Jan 2016
In CYP46A1(-/-) (knockout; KO) slices where endogenous 24S-HC is greatly reduced, NMDAR tone, measured as NMDAR to α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) excitatory post-synaptic current (EPSC) ratio, was reduced.
Cholesterol 24-hydroxylase defect is implicated in memory impairments associated with Alzheimer-like Tau pathology.
Cartier et al., Paris, France. In Hum Mol Genet, Dec 2015
Brain cholesterol is synthesized in situ and cannot cross the blood-brain barrier: to be exported from the central nervous system into the blood circuit, excess cholesterol must be converted to 24S-hydroxycholesterol by the cholesterol 24-hydroxylase encoded by the CYP46A1 gene.
Subpath analysis of each subtype of head and neck cancer based on the regulatory relationship between miRNAs and biological pathways.
Xing et al., Jinan, China. In Oncol Rep, Oct 2015
Our data suggest that human papillomavirus (HPV) is positively correlated with HNSCC in subtype 2. Several miRNAs (miRLet-7A, miR-1, miR-206, miR-153, miR-519A and miR-506) and their target genes (CYP46A1, BPNT1, MCM7 and COL5A1) are crucial for HNSCC prevention via different pathways and may provide further knowledge of the mechanisms involved in the progression of HNSCC.
Chandipura virus perturbs cholesterol homeostasis leading to neuronal apoptosis.
Basu et al., India. In J Neurochem, Oct 2015
In our study of CHPV-infected brain samples, we observed over-expression of genes such as apolipoprotein E, Cyp46a1, Srebf-1 and Nsdhl.
Evidence for altered cholesterol metabolism in Huntington's disease post mortem brain tissue.
Jenner et al., Wollongong, Australia. In Neuropathol Appl Neurobiol, Oct 2015
The level of enzymes that regulate cholesterol homeostasis, cholesterol 24-hydroxylase and delta(24)-sterol reductase were investigated by Western blotting and qPCR in putamen.
Cholesterol hydroperoxides as substrates for cholesterol-metabolizing cytochrome P450 enzymes and alternative sources of 25-hydroxycholesterol and other oxysterols.
Pikuleva et al., Sherbrooke, Canada. In Angew Chem Int Ed Engl, Oct 2015
CYP7A1 and CYP46A1 failed to give metabolites with any of the hydroperoxides.
CYP46A1 inhibition, brain cholesterol accumulation and neurodegeneration pave the way for Alzheimer's disease.
Cartier et al., Orsay, France. In Brain, Aug 2015
To address this issue, we used RNA interference methodology to inhibit the expression of cholesterol 24-hydroxylase, encoded by the Cyp46a1 gene, in the hippocampus of normal mice.
A high-cholesterol diet enriched with polyphenols from Oriental plums (Prunus salicina) improves cognitive function and lowers brain cholesterol levels and neurodegenerative-related protein expression in mice.
Lin et al., Taipei, Taiwan. In Br J Nutr, Jun 2015
Measurements of cognitive function were assessed using the Morris water maze, and the mRNA expression of cholesterol hydroxylase (Cyp46), Aβ and β-secretase 1 (BACE1) were analysed.
Gene expression profiling of cytochromes P450, ABC transporters and their principal transcription factors in the amygdala and prefrontal cortex of alcoholics, smokers and drug-free controls by qRT-PCR.
Gillam et al., Brisbane, Australia. In Xenobiotica, 2014
4. CYP1A1, CYP1B1, CYP2B6, CYP2C8, CYP2C18, CYP2D6, CYP2E1, CYP2J2, CYP2S1, CYP2U1, CYP4X1, CYP46, adrenodoxin and NADPH-P450 reductase, ABCB1, ABCG2, ABCA1, and transcription factors aryl hydrocarbon receptor AhR and proliferator-activated receptor α were quantified in both areas.
Potential diagnostic applications of side chain oxysterols analysis in plasma and cerebrospinal fluid.
Caccia et al., Milano, Italy. In Biochem Pharmacol, 2013
The neurospecific cholesterol 24-hydroxylase converts excess brain cholesterol into 24S-hydroxycholesterol (24OHC) which, via the liver X receptor (LXR), can increase the expression and synthesis of astrocyte ApoE.
CYP46A1 T/C polymorphism associated with the APOE ε4 allele increases the risk of Alzheimer's disease.
Zhou et al., Chongqing, China. In J Neurol, 2013
Studies of the relationship between Alzheimer's disease (AD) and single nucleotide polymorphism (SNP) T/C in intron 2 of the cholesterol-24S-hydroxylase gene (CYP46A1) have reported inconsistent results.
24S-hydroxycholesterol in plasma: a marker of cholesterol turnover in neurodegenerative diseases.
Caccia et al., Milano, Italy. In Biochimie, 2013
Cholesterol is converted into 24S-hydroxycholesterol (24OHC) by cholesterol 24-hydroxylase (CYP46A1) expressed in neural cells.
Cytochrome P450 (CYP) in fish.
Itakura et al., Kōbe, Japan. In Environ Toxicol Pharmacol, 2012
These genes are classified into 18 CYP families: namely, CYP1, CYP2, CYP3, CYP4, CYP5, CYP7, CYP8, CYP11, CYP17, CYP19, CYP20, CYP21, CYP24, CYP26, CYP27, CYP39, CYP46 and CYP51.We pinpointed eight CYP families: namely, CYP1, CYP2, CYP3, CYP4, CYP11, CYP17, CYP19 and CYP26 in this review because these CYP families are studied in detail.
Cytochrome P450s in the synthesis of cholesterol and bile acids--from mouse models to human diseases.
Rozman et al., Ljubljana, Slovenia. In Febs J, 2012
Mouse knockouts of the brain-specific Cyp46a1 have reduced brain cholesterol excretion, whereas, in humans, CYP46A1 polymorphisms associate with cognitive impairment.
Marked change in the balance between CYP27A1 and CYP46A1 mediated elimination of cholesterol during differentiation of human neuronal cells.
Rodrigues et al., Lisbon, Portugal. In Neurochem Int, 2012
Differentiated Ntera2/clone D1 (NT2) cells express the key genes involved in brain cholesterol homeostasis including CYP46A1.
Effect of cholesterol and CYP46 polymorphism on cognitive event-related potentials.
Liu et al., Kao-hsiung, Taiwan. In Psychophysiology, 2011
There was no association between the CYP46 genotype and measures of cognitive event-related potentials.
Quantification of cholesterol-metabolizing P450s CYP27A1 and CYP46A1 in neural tissues reveals a lack of enzyme-product correlations in human retina but not human brain.
Pikuleva et al., Rockville, United States. In J Proteome Res, 2011
The average P450 concentrations/mg of total tissue protein were 345 fmol of CYP46A1 and 110 fmol of CYP27A1 in the temporal lobe, and 60 fmol of CYP46A1 and 490 fmol of CYP27A1 in the retina.
Role of cholesterol 24S-hydroxylase gene polymorphism (rs754203) in primary open angle glaucoma.
El-Shabrawi et al., Graz, Austria. In Mol Vis, 2010
The rs754203 polymorphism itself is unlikely a genetic risk factor for primary open angle glaucoma in Caucasian individuals.
CYP46A1 functional promoter haplotypes decipher genetic susceptibility to Alzheimer's disease.
Song et al., Hong Kong, Hong Kong. In J Alzheimers Dis, 2009
Study of two independent Chinese data sets indicates individuals with CYP46A1 promoter bearing the CG haplotype are genetically more susceptible to Alzheimer's disease than those with TA haplotype.
Cholesterol 24-hydroxylase: an enzyme of cholesterol turnover in the brain.
Kotti et al., Dallas, United States. In Annu Rev Biochem, 2008
Cholesterol 24-hydroxylase is a highly conserved cytochrome P450 that is responsible for the majority of cholesterol turnover in the vertebrate central nervous system.
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