EC Number   |
General Information |
Reference |
|---|
   1.14.14.25 | malfunction |
a single nucleotide polymorphism the in CYP46A1 gene, designated as rs754203, is a risk factor for glaucoma. The enzyme participates to retinal ganglion cell loss under pathophysiological conditions |
727298 |
| 1.14.14.25 | malfunction |
CYP46A1 expression levels are reduced in Huntington's disease. CYP46A1 protein levels are decreased in the putamen, but not cerebral cortex samples, of post-mortem Huntington's disease patients when compared to controls. Huntington's disease is an autosomal dominant neurodegenerative disease caused by abnormal polyglutamine expansion in huntingtin leading to degeneration of striatal neurons. Altered brain cholesterol homeostasis is implicated in Huntington's disease, with increased accumulation of cholesterol in striatal neurons yet reduced levels of cholesterol metabolic precursors |
735877 |
| 1.14.14.25 | malfunction |
disruption of the cholesterol 24-hydroxylase gene causes an 50% decrease in cholesterol turnover, which is compensated for by an equal decrease in the rate of de novo cholesterol synthesis. Mice lacking cholesterol 24-hydroxylase show that whole-body fatty acid and cholesterol metabolism are normal. Profound learning disabilities in cholesterol 24-hydroxylase-deficient mice are often caused by gross anatomical defects in the subregions of the brain implicated in the behavior. A minimal concentration of 0.2 mM geranylgeraniol is required to restore LTP in hippocampal slices from knockout mice |
701715 |
| 1.14.14.25 | malfunction |
knocking down CYP46A1 expression in the striatum, via an adeno-associated virus-mediated delivery of selective shCYP46A1, reproduced the Huntingtons disease phenotype, with spontaneous striatal neuron degeneration and motor deficits. CYP46A1 expression levels are reduced in Huntington's disease. In the R6/2 Huntington's disease mouse model, adeno-associated virus-mediated delivery of CYP46A1 into the striatum decreases neuronal atrophy, decreases the number, intensity level and size of expansion in huntingtin aggregates and improves motor deficits, as assessed by rotarod and clasping behavioural tests. Adeno-associated virus-CYP46A1 infection in R6/2 mice also restores levels of cholesterol and lanosterol and increases levels of desmosterol |
-, 735877 |
| 1.14.14.25 | malfunction |
polymorphisms in the CYP46 gene and CYP46A1 enzyme dysfunction are involved in neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease. The 24(S)-hydroxycholesterol levels in cerebrospinal fluid are higher in patients with Alzheimer's disease compared to healthy control. CYP46A1 inhibition by voriconazole decreases 24S-hydroxycholesterol levels in the retina and affects cholesterol homeostasis and function in the retina |
736072 |
| 1.14.14.25 | metabolism |
cholesterol 24S-hydroxylase is a cholesterol metabolic enzyme with regulatory function in traumatic brain injury, overview |
711641 |
| 1.14.14.25 | metabolism |
CYP46A1 gene variations (rs7157609 and rs4900442) influence the risk factor for Alzheimer's disease via an influence on brain cholesterol metabolism, especially the interaction term of both SNPs and the resulting haplotype reveal a strong association with the risk of Alzheimers disease |
703580 |
| 1.14.14.25 | more |
Cyp46 is upregulated in traumatic brain injury. Membrane damage during traumatic brain injury alters the brain homeostasis of cholesterol and other lipids. Reaction product 24S-hydroxycholesterol decreases mRNA levels of the cholesterol synthesis genes HMG CoA reductase, squalene synthase, and FPP synthase but does not alter levels of the mRNA of fatty acid synthesis genes acetyl CoA carboxylase or fatty acid synthase |
711641 |
| 1.14.14.25 | more |
increased expression of cholesterol 24S-hydroxylase in brain results in disruption of glial glutamate transporter EAAT2 association with lipid rafts with a potential role in Alzheimers disease, overview |
712816 |
| 1.14.14.25 | more |
mapping of the binding region for CYP46A1 redox partner oxidoreductase and identification of allosteric and redox partner binding sites which share a common border, by using a combination of hydrogen-deuterium exchange coupled to mass spectrometry, computational modeling, site-directed mutagenesis, and analysis of the CYP46A1 crystal structure, overview. Residues K422 and R424 are important for enzyme activity |
736502 |
