CYP46A1

Summary

Gene Symbol: CYP46A1
Description: cytochrome P450, family 46, subfamily A, polypeptide 1
Alias: CP46, CYP46, CH24H, cholesterol 24-hydroxylase, cytochrome P450 46A1, cytochrome P450, subfamily 46 (cholesterol 24-hydroxylase)
Species: human

Top Publications

  1. ncbi Crystal structures of substrate-bound and substrate-free cytochrome P450 46A1, the principal cholesterol hydroxylase in the brain
    Natalia Mast
    Department of Pharmacology and Toxicology, The Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, Galveston, TX 77555, USA
    Proc Natl Acad Sci U S A 105:9546-51. 2008
  2. ncbi Primary open-angle glaucoma: association with cholesterol 24S-hydroxylase (CYP46A1) gene polymorphism and plasma 24-hydroxycholesterol levels
    Cynthia Fourgeux
    Eye and Nutrition Research Group, UMR1129 FLAVIC Flaveur, vision et comportement du consommateur Flavor, Vision, and Consumer Behavior, INRA French National Institute for Agricultural Research, Dijon, France
    Invest Ophthalmol Vis Sci 50:5712-7. 2009
  3. ncbi Cholesterol homeostasis in human brain: turnover of 24S-hydroxycholesterol and evidence for a cerebral origin of most of this oxysterol in the circulation
    I Bjorkhem
    Division of Clinical Chemistry, Karolinska Institute, Huddinge University Hospital, Sweden
    J Lipid Res 39:1594-600. 1998
  4. ncbi Polymorphism in the cholesterol 24S-hydroxylase gene is associated with Alzheimer's disease
    Heike Kolsch
    Department of Psychiatry, University of Bonn, Sigmund Freud Strasse 25, 53105 Bonn, Germany
    Mol Psychiatry 7:899-902. 2002
  5. ncbi Association between a T/C polymorphism in intron 2 of cholesterol 24S-hydroxylase gene and Alzheimer's disease in Chinese
    Binbin Wang
    Center for Human and Animal Genetics, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China
    Neurosci Lett 369:104-7. 2004
  6. ncbi Genetic association of CYP46 and risk for Alzheimer's disease
    Onofre Combarros
    Neurology Service, Marqués de Valdecilla University Hospital University of Cantabria, Santander, Spain
    Dement Geriatr Cogn Disord 18:257-60. 2004
  7. ncbi CYP46: a risk factor for Alzheimer's disease or a coincidence?
    Ewa Golanska
    Department of Molecular Pathology and Neuropathology, Medical University of Lodz, Poland
    Neurosci Lett 383:105-8. 2005
  8. ncbi Intron 2 (T/C) CYP46 polymorphism is associated with Alzheimer's disease in Chinese patients
    Y Li
    Department of Biochemistry, University of Hong Kong, Hong Kong, SAR, China
    Dement Geriatr Cogn Disord 22:399-404. 2006
  9. ncbi Increased brain beta-amyloid load, phosphorylated tau, and risk of Alzheimer disease associated with an intronic CYP46 polymorphism
    Andreas Papassotiropoulos
    Division of Pychiatry Research, University of Zurich, Switzerland
    Arch Neurol 60:29-35. 2003
  10. ncbi Intronic CYP46 polymorphism along with ApoE genotype in sporadic Alzheimer Disease: from risk factors to disease modulators
    Barbara Borroni
    Neurologic Clinic, University of Brescia, Spedali Civili de Brescia, Piazzale Spedali Civili 1, Brescia 25123, Italy
    Neurobiol Aging 25:747-51. 2004

Research Grants

  1. Cholesterol metabolizing P450s: structure and function
    Irina Pikuleva; Fiscal Year: 2009
  2. Cholesterol metabolizing P450s: structure and function
    Irina Pikuleva; Fiscal Year: 2009
  3. Cholesterol metabolizing P450s: structure and function
    Irina A Pikuleva; Fiscal Year: 2010
  4. Significance of CYP46A1 and other P450s in retinal function
    Irina Pikuleva; Fiscal Year: 2009
  5. Significance of CYP46A1 and other P450s in retinal function
    Irina A Pikuleva; Fiscal Year: 2010
  6. Significance of CYP46A1 and other P450s in retinal function
    Irina Pikuleva; Fiscal Year: 2009
  7. Cholesterol and Sphingolipid Metabolism in Alzheimer's Disease
    Ta Yuan Chang; Fiscal Year: 2010
  8. Fatty Acid Synthesis in Specific Hypothalamic Neurons: Control of Appetite and En
    Joseph Goldstein; Fiscal Year: 2007
  9. Cyp46 regulation of cholesterol efflux and ABeta
    CASANDRA CARTAGENA; Fiscal Year: 2007
  10. Biomarkers in Aging, MCI and Alzheimer's Disease
    Douglas Galasko; Fiscal Year: 2007

Scientific Experts

Detail Information

Publications104 found, 100 shown here

  1. ncbi Crystal structures of substrate-bound and substrate-free cytochrome P450 46A1, the principal cholesterol hydroxylase in the brain
    Natalia Mast
    Department of Pharmacology and Toxicology, The Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, Galveston, TX 77555, USA
    Proc Natl Acad Sci U S A 105:9546-51. 2008
    By converting cholesterol to 24S-hydroxycholesterol, cytochrome P450 46A1 (CYP46A1) initiates the major pathway for cholesterol removal from the brain. Two crystal structures of CYP46A1 were determined. First is the 1...
  2. ncbi Primary open-angle glaucoma: association with cholesterol 24S-hydroxylase (CYP46A1) gene polymorphism and plasma 24-hydroxycholesterol levels
    Cynthia Fourgeux
    Eye and Nutrition Research Group, UMR1129 FLAVIC Flaveur, vision et comportement du consommateur Flavor, Vision, and Consumer Behavior, INRA French National Institute for Agricultural Research, Dijon, France
    Invest Ophthalmol Vis Sci 50:5712-7. 2009
    ..Cholesterol-24S-hydroxylase (CYP46A1) is a cholesterol-metabolizing enzyme that is especially expressed in retinal ganglion cells...
  3. ncbi Cholesterol homeostasis in human brain: turnover of 24S-hydroxycholesterol and evidence for a cerebral origin of most of this oxysterol in the circulation
    I Bjorkhem
    Division of Clinical Chemistry, Karolinska Institute, Huddinge University Hospital, Sweden
    J Lipid Res 39:1594-600. 1998
    ..The possibility is discussed that circulating levels of 24S-hydroxycholesterol can be used as a marker for pathological and/or developmental changes in the brain...
  4. ncbi Polymorphism in the cholesterol 24S-hydroxylase gene is associated with Alzheimer's disease
    Heike Kolsch
    Department of Psychiatry, University of Bonn, Sigmund Freud Strasse 25, 53105 Bonn, Germany
    Mol Psychiatry 7:899-902. 2002
    ..The enzyme catalyzing the conversion of cholesterol to 24S-hydroxycholesterol, cholesterol 24S-hydroxylase (CYP46), is mainly expressed in neurons...
  5. ncbi Association between a T/C polymorphism in intron 2 of cholesterol 24S-hydroxylase gene and Alzheimer's disease in Chinese
    Binbin Wang
    Center for Human and Animal Genetics, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China
    Neurosci Lett 369:104-7. 2004
    A polymorphism (T/C) in intron 2 of the cholesterol 24-hydroxylase (CYP46) gene has recently been reported to be associated with the risk for late-onset Alzheimer's disease (LOAD)...
  6. ncbi Genetic association of CYP46 and risk for Alzheimer's disease
    Onofre Combarros
    Neurology Service, Marqués de Valdecilla University Hospital University of Cantabria, Santander, Spain
    Dement Geriatr Cogn Disord 18:257-60. 2004
    ..brain cholesterol is its conversion into the 24S-hydroxycholesterol catalyzed by cholesterol 24S-hydroxylase (CYP46)...
  7. ncbi CYP46: a risk factor for Alzheimer's disease or a coincidence?
    Ewa Golanska
    Department of Molecular Pathology and Neuropathology, Medical University of Lodz, Poland
    Neurosci Lett 383:105-8. 2005
    Excess cholesterol is removed from the brain via hydroxylation mediated by cholesterol 24S-hydroxylase (CYP46)...
  8. ncbi Intron 2 (T/C) CYP46 polymorphism is associated with Alzheimer's disease in Chinese patients
    Y Li
    Department of Biochemistry, University of Hong Kong, Hong Kong, SAR, China
    Dement Geriatr Cogn Disord 22:399-404. 2006
    ..Genetic association of CYP46A1 polymorphisms with AD had been under extensive investigations; however, observations on intron 2 T-->C (rs754203) ..
  9. ncbi Increased brain beta-amyloid load, phosphorylated tau, and risk of Alzheimer disease associated with an intronic CYP46 polymorphism
    Andreas Papassotiropoulos
    Division of Pychiatry Research, University of Zurich, Switzerland
    Arch Neurol 60:29-35. 2003
    b>CYP46, the gene encoding cholesterol 24-hydroxylase, plays a key role in the hydroxylation of cholesterol and thereby mediates its removal from brain.
  10. ncbi Intronic CYP46 polymorphism along with ApoE genotype in sporadic Alzheimer Disease: from risk factors to disease modulators
    Barbara Borroni
    Neurologic Clinic, University of Brescia, Spedali Civili de Brescia, Piazzale Spedali Civili 1, Brescia 25123, Italy
    Neurobiol Aging 25:747-51. 2004
    ..elimination involves two mechanisms dependent on Apolipoprotein E (ApoE) and cholesterol 24-hydroxylase (CYP46)...
  11. ncbi The effect of 24S-hydroxycholesterol on cholesterol homeostasis in neurons: quantitative changes to the cortical neuron proteome
    Yuqin Wang
    Institute of Mass Spectrometry, School of Medicine, Swansea University, Singleton Park, Swansea, SA2 8PP, UK
    J Proteome Res 7:1606-14. 2008
    ..represents the major metabolic product of cholesterol in brain, being formed via the cytochrome P450 (CYP) enzyme CYP46A1. CYP46A1 is expressed exclusively in brain, normally by neurons...
  12. ncbi Reduction in levels of 24S-hydroxycholesterol by statin treatment in patients with Alzheimer disease
    Gloria Lena Vega
    Department of Clinical Nutrition, The Center for Human Nutrition, University of Texas Southwestern Medical Center and Nutrition and Metabolism Laboratory, Veterans Affairs Medical Center, Dallas 75390, USA
    Arch Neurol 60:510-5. 2003
    ..cholesterol from damaged or dying neurons is converted to 24S-hydroxycholesterol by cholesterol 24-hydroxylase (CYP46)...
  13. ncbi Convergence of genes implicated in Alzheimer's disease on the cerebral cholesterol shuttle: APP, cholesterol, lipoproteins, and atherosclerosis
    C J Carter
    Neurochem Int 50:12-38. 2007
    ..ABCA1, ABCA2, lipoprotein receptors LDLR, LRP1, LRP8 and VLDLR, and the cholesterol metabolising enzymes CYP46A1 and CH25H, whose oxysterol products activate the liver X receptor NR1H2 and are metabolised to esters by SOAT1...
  14. ncbi Steroid and protein ligand binding to cytochrome P450 46A1 as assessed by hydrogen-deuterium exchange and mass spectrometry
    Wei Li Liao
    Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, Rockville, Maryland 20850, USA
    Biochemistry 48:4150-8. 2009
    b>Cytochrome P450 46A1 (CYP46A1) is a key enzyme responsible for cholesterol elimination from the brain. This P450 can interact with different steroid substrates and protein redox partners...
  15. ncbi Structural basis of drug binding to CYP46A1, an enzyme that controls cholesterol turnover in the brain
    Natalia Mast
    Department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, Ohio 44106, USA
    J Biol Chem 285:31783-95. 2010
    b>Cytochrome P450 46A1 (CYP46A1) initiates the major pathway of cholesterol elimination from the brain and thereby controls cholesterol turnover in this organ...
  16. ncbi Modifications of the expression of genes involved in cerebral cholesterol metabolism in the rat following chronic ingestion of depleted uranium
    Radjini Racine
    Institute for Radiological Protection and Nuclear Safety, Radiological Protection and Human Health Division, Radiobiology and Epidemiology Department, Laboratory of Experimental Nuclear Toxicology, BP no 17, F 92262, Fontenay aux Roses Cedex, France
    J Mol Neurosci 38:159-65. 2009
    ..The study focuses on gene expression. Cholesterol-catabolizing enzyme CYP46A1 displayed a 39% increase of its messenger RNA (mRNA) level...
  17. ncbi Studies on the transcriptional regulation of cholesterol 24-hydroxylase (CYP46A1): marked insensitivity toward different regulatory axes
    Yoshihiko Ohyama
    Divisions of Clinical Chemistry and Clinical Pharmacology, Department of Laboratory Medicine, Karolinska University Hospital, Huddinge, Stockholm, Sweden
    J Biol Chem 281:3810-20. 2006
    ..Conversion of cholesterol into 24S-hydroxycholesterol by the cholesterol 24-hydroxylase (CYP46A1) is the quantitatively most important mechanism...
  18. ncbi Brain cholesterol turnover required for geranylgeraniol production and learning in mice
    Tiina J Kotti
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA
    Proc Natl Acad Sci U S A 103:3869-74. 2006
    ..We conclude that cholesterol turnover in brain activates the mevalonate pathway and that a constant production of geranylgeraniol in a small subset of neurons is required for LTP and learning...
  19. ncbi Increased expression of cholesterol 24S-hydroxylase results in disruption of glial glutamate transporter EAAT2 association with lipid rafts: a potential role in Alzheimer's disease
    Guilian Tian
    Department of Neuroscience, The Ohio State University, Columbus, Ohio 43210, USA
    J Neurochem 113:978-89. 2010
    ..In AD brains, cholesterol 24S-hydroxylase (CYP46), a key enzyme in maintenance of cholesterol homeostasis in the brain, is markedly increased in astrocytes but ..
  20. ncbi Oxysterols: functional significance in fetal development and the maintenance of normal retinal function
    Norman B Javitt
    New York University School of Medicine, New York, New York, USA
    Curr Opin Lipidol 18:283-8. 2007
    ..Recent findings extend the biologic activities of oxysterols as ligands for nuclear receptors to a role in morphogenesis during fetal development and to a role in the metabolism of photooxidation products of cholesterol in the retina...
  21. ncbi A mouse model for alpha-methylacyl-CoA racemase deficiency: adjustment of bile acid synthesis and intolerance to dietary methyl-branched lipids
    Kalle Savolainen
    Department of Biochemistry, Biocenter Oulu, University of Oulu, FIN 90014, Finland
    Hum Mol Genet 13:955-65. 2004
    ..This enzyme can be placed, together with CYP3A11 and CYP46A1, to make an Amacr-independent pathway for the generation of C24 bile acids...
  22. ncbi The use of the Dhcr7 knockout mouse to accurately determine the origin of fetal sterols
    G S Tint
    Research Service, Department of Veterans Affairs Medical Center, East Orange, NJ 07018, USA
    J Lipid Res 47:1535-41. 2006
    ..The early fetal brain also appears to conserve cholesterol by keeping cholesterol 24-hydroxylase expression low until approximately E18...
  23. ncbi Neuronal expression and subcellular localization of cholesterol 24-hydroxylase in the mouse brain
    Denise M O Ramirez
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    J Comp Neurol 507:1676-93. 2008
    Cholesterol 24-hydroxylase is a cytochrome P450 (CYP46A1) that is selectively expressed in the brain and is responsible for the majority of cholesterol turnover in the central nervous system...
  24. ncbi Regulation of alpha- and beta-secretase activity by oxysterols: cerebrosterol stimulates processing of APP via the alpha-secretase pathway
    D Famer
    Division of Clinical Geriatrics, Department of Neurobiology Care Sciences and Society, Karolinska Institutet and Karolinska University, Hospital Huddinge, 14186 Stockholm, Sweden
    Biochem Biophys Res Commun 359:46-50. 2007
    ..Polymorphisms within the CYP46A1 gene have been associated with Alzheimer's disease (AD) incidence...
  25. ncbi Knockout of the cholesterol 24-hydroxylase gene in mice reveals a brain-specific mechanism of cholesterol turnover
    Erik G Lund
    Department of Molecular Genetics, The University of Texas Southwestern Medical Center, Dallas, Texas 75390 9046, USA
    J Biol Chem 278:22980-8. 2003
    ..An example of the latter type of enzyme is cholesterol 24-hydroxylase, a cytochrome P450 (CYP46A1) that is expressed at 100-fold higher levels in the brain than in the liver...
  26. ncbi Sp proteins play a critical role in histone deacetylase inhibitor-mediated derepression of CYP46A1 gene transcription
    Maria João Nunes
    Faculty of Pharmacy, iMed UL Research Institute for Medicines and Pharmaceutical Sciences, University of Lisbon, 1649 003 Lisbon, Portugal
    J Neurochem 113:418-31. 2010
    We investigated whether the CYP46A1 gene, a neuronal-specific cytochrome P450, responsible for the majority of brain cholesterol turnover, is subject to transcriptional modulation through modifications in histone acetylation...
  27. ncbi Plasma 24S hydroxycholesterol response to statins in Alzheimer's disease patients: effects of gender, CYP46, and ApoE polymorphisms
    Gloria Lena Vega
    The Nutrition and Metabolism Laboratory, Metabolic Unit, Veterans Affairs Medical Center, Dallas, TX 75390, USA
    J Mol Neurosci 33:51-5. 2007
    ..Brain cholesterol is converted to 24-S-hydroxycholesterol, a reaction catalyzed by CYP46. The oxysterol traverses the blood-brain barrier and is transported to the liver by plasma lipoproteins...
  28. ncbi [Cholesterol and statins in Alzheimer disease]
    Gerhard Ransmayr
    Neurologisch psychiatrische Abteilung, Allgemeines Krankenhauses der Stadt Linz, Krankenhausstrasse 9, A 4020 Linz
    Wien Med Wochenschr 153:258-9. 2003
    ..In two further studies a polymorphism in the CYP46 gene encoding the cholesterol-24 hydroxylase was found to be associated with a significant increase in the risk of ..
  29. ncbi Xenobiotic-metabolizing enzymes and transporters in the normal human brain: regional and cellular mapping as a basis for putative roles in cerebral function
    Fabien Dutheil
    Universite Paris Descartes, Paris, France
    Drug Metab Dispos 37:1528-38. 2009
    ..profile of seven ABC transporters (ABCB1, ABCC1-C5, and ABCG2), 24 P450s (CYP1, CYP2, and CYP3 families and CYP46A1), and 14 related transcription factors [aryl hydrocarbon receptor, nuclear receptor (NR)1I2/pregnane X receptor, ..
  30. ncbi Statin-like drugs for the treatment of brain cholesterol loss in Alzheimer's disease
    Elisa Biondi
    Universita degli Studi di Torino, Torino, Italy
    Curr Drug Saf 2:173-6. 2007
    ..in some cholesterol related genes like the allele epsilon4 of the apolipoprotein E, cholesterol 24-hydroxylase (CYP46A1), ATP-binding cassette transporter a1 (ABCA1) and the lipoprotein receptor-related protein (LRP)...
  31. ncbi Cholesterol 24-hydroxylase: an enzyme of cholesterol turnover in the brain
    David W Russell
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
    Annu Rev Biochem 78:1017-40. 2009
    ..This review focuses on how the link between cholesterol metabolism and higher-order brain function was experimentally established...
  32. ncbi The cellular biochemistry of cholesterol and statins: insights into the pathophysiology and therapy of Alzheimer's disease
    Benjamin Wolozin
    Department of Pharmacology, Loyola University Medical Center, Bldg 102, Rm 3634, 2160 South First Ave, Maywood, IL 60153, USA
    CNS Drug Rev 10:127-46. 2004
    ..These genes include apolipoprotein E, cholesterol 24 hydroxylase (Cyp46), acyl-CoA:cholesterol acetyltransferase (ACAT), and the cholesterol transporter ABCA1...
  33. ncbi Oxysterols as markers of neurological disease--a review
    Valerio Leoni
    Division of Biochemistry and Genetics, National Institute of Neurology C Besta, Milan, Italy
    Scand J Clin Lab Invest 69:22-5. 2009
    ..cholesterol is converted into the more hydrophilic oxysterol 24S-hydroxycholesterol by the neuron-specific enzyme CYP46A1. About 99% of the total excretion of this oxysterol by the brain occurs across the blood-brain barrier directly ..
  34. ncbi 24S-hydroxycholesterol in relation to disease manifestations of acute experimental autoimmune encephalomyelitis
    C E Teunissen
    Department of Molecular Cell Biology, VU University Medical Center, Amsterdam, The Netherlands
    J Neurosci Res 85:1499-505. 2007
    ..Immunostaining of the 24S-hydroxycholesterol-forming enzyme Cyp46 was shown in macrophage infiltrates...
  35. ncbi Cholesterol metabolism in the brain: importance of 24S-hydroxylation
    D Lutjohann
    Department of Clinical Pharmacology, University of Bonn, Germany
    Acta Neurol Scand Suppl 185:33-42. 2006
    ..The enzyme (CYP46a1) mediating this conversion has been characterized at the molecular level and is mainly located in neurons...
  36. ncbi Cholesterol efflux as a critical component of Alzheimer's disease pathogenesis
    G William Rebeck
    Georgetown University School of Medicine, Washington, DC 20007, USA
    J Mol Neurosci 23:219-24. 2004
    ..In the brain, cholesterol is converted to 24S hydroxycholesterol by the enzyme Cyp46. 24S hydroxycholesterol promotes gene transcription through interactions with LXR...
  37. ncbi ABCA2 is a strong genetic risk factor for early-onset Alzheimer's disease
    Sandrine Mace
    Aventis Pharma, Evry Genetics Center and Neurodegenerative Disease Group, Paris Research Center, 94400 Vitry sur Seine, France
    Neurobiol Dis 18:119-25. 2005
    ..However, together with the reported associations of AD with APOE, CYP46A1 and ABCA1, the present result adds a very significant support for the role of cholesterol and phospholipid ..
  38. ncbi Cholesterol in neurologic disorders of the elderly: stroke and Alzheimer's disease
    Allison B Reiss
    Department of Medicine, New York University School of Medicine, New Bellevue 16N1, 550 First Avenue, New York, NY 10016, USA
    Neurobiol Aging 25:977-89. 2004
    ..The reduction in stroke and AD risk in patients treated with cholesterol-lowering statins is also discussed...
  39. ncbi PRND 3'UTR polymorphism may be associated with behavioral disturbances in Alzheimer disease
    Marcin Flirski
    Department of Old Age Psychiatry and Psychotic Disorders, Medical University of Lodz, Lodz, Poland
    Prion 6:73-80. 2012
    ..In this research paper, our aim is to evaluate the association between the APOE, CYP46, PRNP and PRND genes and the profile of neuropsychiatric symptoms in Polish subjects with AD and mild cognitive ..
  40. ncbi Cholesterol 25-hydroxylation activity of CYP3A
    Akira Honda
    Department of Gastroenterology, Center for Collaborative Research, Ibaraki 300 0395, Japan
    J Lipid Res 52:1509-16. 2011
    ..This oxysterol is also synthesized by sterol 27-hydroxylase (CYP27A1) and cholesterol 24-hydroxylase(CYP46A1), but it is only a minor product of these enzymes...
  41. ncbi Adeno-associated virus gene therapy with cholesterol 24-hydroxylase reduces the amyloid pathology before or after the onset of amyloid plaques in mouse models of Alzheimer's disease
    Eloise Hudry
    INSERM U745, University Paris Descartes, Faculte des Sciences Pharmaceutiques et Biologiques, Paris, France
    Mol Ther 18:44-53. 2010
    ..is 24S-hydroxycholesterol, an oxysterol generated by the neuronal cholesterol 24-hydroxylase encoded by the CYP46A1 gene...
  42. ncbi A CYP46 T/C SNP modulates parahippocampal and hippocampal morphology in young subjects
    Jürgen Hänggi
    Division of Neuropsychology, Institute of Psychology, University of Zurich, Binzmühlestr 14 25, 8050 Zurich, Switzerland
    Neurobiol Aging 32:1023-32. 2011
    ..Previous data showed that brain ?-amyloid load in elderly subjects with the CYP46 (cholesterol 24S-hydroxylase) TT-positive genotype was higher than in CYP46 TT-negative elderly subjects...
  43. ncbi cDNA cloning of cholesterol 24-hydroxylase, a mediator of cholesterol homeostasis in the brain
    E G Lund
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75235 9046, USA
    Proc Natl Acad Sci U S A 96:7238-43. 1999
    ..are localized to the endoplasmic reticulum, share 95% identity, and represent a new cytochrome P450 subfamily (CYP46)...
  44. ncbi 24(S)-hydroxycholesterol induces neuronal cell death through necroptosis, a form of programmed necrosis
    Kazunori Yamanaka
    Systems Life Sciences, Department of Medical Life Systems, Faculty of Medical and Life Sciences, Doshisha University, Kyoto 610 0394, Japan
    J Biol Chem 286:24666-73. 2011
    ..Collectively, these results suggest that 24S-OHC induces neuronal cell death by necroptosis, a form of programmed necrosis...
  45. ncbi The antifungal drug voriconazole is an efficient inhibitor of brain cholesterol 24S-hydroxylase in vitro and in vivo
    Marjan Shafaati
    Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institute, Huddinge, Sweden
    J Lipid Res 51:318-23. 2010
    ..Crystal structures of substrate-bound and substrate-free cytochrome P450 46A1, the principal cholesterol hydroxylase in the brain. Proc. Natl. Acad. Sci. USA. 2008. 105: 9546-9551)...
  46. ncbi The cytochrome P450 (CYP) gene superfamily in Daphnia pulex
    William S Baldwin
    Clemson University, Biological Sciences, Institute of Environmental Toxicology, Pendleton, SC, USA
    BMC Genomics 10:169. 2009
    ..The latter form a critical component of detoxification systems...
  47. ncbi Earlier onset of Alzheimer's disease: risk polymorphisms within PRNP, PRND, CYP46, and APOE genes
    Ewa Golanska
    Department of Molecular Pathology and Neuropathology, Medical University of Lodz, Lodz, Poland
    J Alzheimers Dis 17:359-68. 2009
    We studied eight polymorphisms within APOE, PRNP, PRND, and CYP46 genes in 213 Polish late-onset patients with Alzheimer's disease (AD) and 171 non-demented elderly controls...
  48. ncbi Effect of cholesterol and CYP46 polymorphism on cognitive event-related potentials
    Chiou Lian Lai
    Department of Neurology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Taiwan
    Psychophysiology 48:1572-7. 2011
    The integrated effect of the cholesterol and CYP46 genotypes on the risk of cognitive decline needs to be determined...
  49. ncbi Neuronal differentiation alters the ratio of Sp transcription factors recruited to the CYP46A1 promoter
    Inês Milagre
    Research Institute for Medicines and Pharmaceutical Sciences iMED UL, University of Lisbon, Lisbon, Portugal
    J Neurochem 120:220-9. 2012
    b>CYP46A1 is a neuron-specific cytochrome P450 that plays a pivotal role in maintaining cholesterol homeostasis in the CNS...
  50. ncbi Cholesterol 24-hydroxylase (CYP46A1) polymorphisms are associated with faster cognitive deterioration in Chinese older persons: a two-year follow up study
    Brenda Yan Fu
    Department of Psychiatry, The Chinese University of Hong Kong, Hong Kong SAR, China
    Int J Geriatr Psychiatry 24:921-6. 2009
    We previously found that the polymorphisms of cholesterol 24-hydroxylase (CYP46A1) gene were associated with the risk of Alzheimer's disease (AD) in Chinese...
  51. ncbi Reduction of cholesterol synthesis in the mouse brain does not affect amyloid formation in Alzheimer's disease, but does extend lifespan
    Rebekkah W Halford
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
    Proc Natl Acad Sci U S A 106:3502-6. 2009
    ..These studies suggest that reducing de novo cholesterol synthesis in the brain will not substantially alter the course of Alzheimer's disease, but may confer a survival advantage...
  52. ncbi Liver X receptor activation enhances cholesterol loss from the brain, decreases neuroinflammation, and increases survival of the NPC1 mouse
    Joyce J Repa
    Department of Internal Medicine, University of Texas Southwestern Medical School, Dallas, Texas 75390 9151, USA
    J Neurosci 27:14470-80. 2007
    ..or expression of genes associated with the formation of 24(S)-hydroxycholesterol or neurosteroids such as CYP46A1, 3alphaHSD, and CYP11A1...
  53. ncbi 24S-hydroxycholesterol and cholesterol-24S-hydroxylase (CYP46A1) in the retina: from cholesterol homeostasis to pathophysiology of glaucoma
    Cynthia Fourgeux
    Centre des Sciences du Gout et de l Alimentation, UMR 1324 INRA, 6265 CNRS, University of Burgundy, Centre de Recherche INRA, Dijon, France
    Chem Phys Lipids 164:496-9. 2011
    ..the role of cholesterol and cholesterol metabolism therein, with special emphasis on cholesterol-24S-hydroxylase (CYP46A1)...
  54. ncbi 24S-hydroxycholesterol effects on lipid metabolism genes are modeled in traumatic brain injury
    CASANDRA M CARTAGENA
    Department of Neuroscience, Georgetown University Medical Center, 3970 Reservoir Road, NW, Washington, DC 20057, USA
    Brain Res 1319:1-12. 2010
    ..Cholesterol 24S-hydroxylase (Cyp46) is a cholesterol metabolic enzyme that is increased after TBI...
  55. ncbi Brain injury induces cholesterol 24-hydroxylase (Cyp46) expression in glial cells in a time-dependent manner
    Kosara Smiljanic
    Department of Neurobiology, Institute for Biological Research Sinisa Stankovic, University of Belgrade, Belgrade, Serbia
    Histochem Cell Biol 134:159-69. 2010
    ..The enzyme responsible for elimination of cholesterol excess from the brain is cholesterol 24-hydroxylase (Cyp46)...
  56. ncbi Quercetin activates AMP-activated protein kinase by reducing PP2C expression protecting old mouse brain against high cholesterol-induced neurotoxicity
    Jun Lu
    Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Xuzhou Normal University, Xuzhou 221116, Jiangsu Province, P R China
    J Pathol 222:199-212. 2010
    ..of high-cholesterol-fed old mice, which reduced cholesterol levels, down-regulated cholesterol 24-hydroxylase (CYP46A1) and beta-amyloid converting enzyme 1 (BACE1) expression, decreased eukaryotic translation initiation factor ..
  57. ncbi CYP46A1 functional promoter haplotypes decipher genetic susceptibility to Alzheimer's disease
    Yan Li
    Department of Biochemistry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
    J Alzheimers Dis 21:1311-23. 2010
    We here demonstrate that promoter polymorphisms rs8003602 and rs3783320 of cholesterol 24S-hydroxylase (CYP46A1) were significantly associated with Alzheimer's disease (AD) in Chinese subjects...
  58. ncbi Capillary cerebral amyloid angiopathy identifies a distinct APOE epsilon4-associated subtype of sporadic Alzheimer's disease
    Dietmar Rudolf Thal
    Institute of Pathology, University of Ulm, Albert Einstein Allee 11, Ulm, Germany
    Acta Neuropathol 120:169-83. 2010
    ....
  59. ncbi Chromatin-modifying agents increase transcription of CYP46A1, a key player in brain cholesterol elimination
    Inês Milagre
    iMed UL Research Institute for Medicines and Pharmaceutical Sciences, Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal
    J Alzheimers Dis 22:1209-21. 2010
    ..major mechanism of brain cholesterol elimination is the conversion of cholesterol into 24S-hydroxycholesterol by CYP46A1, a neuron-specific cytochrome P450...
  60. ncbi 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
    Wei Li Liao
    Institute for Bioscience and Biotechnology Research, Rockville, Maryland 20850, USA
    J Proteome Res 10:241-8. 2011
    ..a multiple reaction monitoring (MRM) workflow for measurements of low-abundance membrane proteins, we quantified CYP46A1 and CYP27A1 in human brain and retina samples from four donors...
  61. ncbi Distribution of cholesterol 24-hydroxylase in the monkey brain
    Xin He
    Department of Anatomy, Beijing University of Chinese Medicine, Beijing 100029, China
    Neurosci Bull 26:197-204. 2010
    ..The present study aimed to elucidate the distribution of cholesterol 24-hydroxylase in the monkey brain...
  62. ncbi Marked variability in hepatic expression of cytochromes CYP7A1 and CYP27A1 as compared to cerebral CYP46A1. Lessons from a dietary study with omega 3 fatty acids in hamsters
    Natalia Mast
    Department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, OH, USA
    Biochim Biophys Acta 1801:674-81. 2010
    ..CYP27A1 and CYP46A1 mRNA levels were increased in the liver and brain, respectively, whereas possible effects on CYP7A1 were obscured ..
  63. ncbi Comparative analysis of human embryonic stem cell and induced pluripotent stem cell-derived hepatocyte-like cells reveals current drawbacks and possible strategies for improved differentiation
    Justyna Jozefczuk
    Molecular Embryology and Aging Group, Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany
    Stem Cells Dev 20:1259-75. 2011
    ..among the cytochrome P450 gene family, CYP19A1, CYP1A1, and CYP11A1 were enriched in hESC-derived HLCs, and CYP46A1 and CYP26A1 in iPSC-derived HLCs...
  64. ncbi Enhanced production of 24S-hydroxycholesterol is not sufficient to drive liver X receptor target genes in vivo
    M Shafaati
    Divisions of Clinical Chemistry and Clinical Research Center, Department of Laboratory Medicine, Karolinska University Hospital Huddinge, Huddinge, Sweden
    J Intern Med 270:377-87. 2011
    ..24S-OHC is one of the most efficient endogenous LXR agonists known and is present in the brain and in the circulation at relatively high levels...
  65. ncbi Cellular stress from excitatory neurotransmission contributes to cholesterol loss in hippocampal neurons aging in vitro
    Alejandro O Sodero
    VIB Department of Molecular and Developmental Genetics, Katholieke Universiteit Leuven, Leuven, Belgium
    Neurobiol Aging 32:1043-53. 2011
    ..vitro aging is paralleled by upregulation and translocation to the neuronal surface of cholesterol-24-hydroxylase (Cyp46), the enzyme responsible for cholesterol removal from neurons...
  66. ncbi [Cytochrome P450 isoenzymes in metabolism of endo- and exogenic compounds]
    Anita Wisniewska
    Department of Pharmaceutical Technology and Biochemistry, Chemical Faculty, Gdansk University of Technology, 11 12 Narutowicza St, 80 233 Gdansk, Poland
    Postepy Biochem 55:259-71. 2009
    ..CYP51A1 is crucial for sterol biosynthesis, whereas CYP7A1, 7B1 and 39A1 take part in synthesis of bile acids and CYP46A1 in metabolism of cholesterol. Therapeutic agents are metabolised mainly by CYP3A4, 2D6, 2C9 and 2C19...
  67. ncbi Oxysterols as biomarkers in neurodegenerative diseases
    Valerio Leoni
    Genetic of neurodegenerative and metabolic diseases Unit, IRCCS National Institute of Neurology C Besta, Milano, Italy
    Chem Phys Lipids 164:515-24. 2011
    ..homeostasis, excess of cholesterol is converted into 24OHC by the neuronal specific cholesterol 24-hydroxylase (CYP46A1). The brain is the major source of circulating 24OHC...
  68. ncbi Cyp46 polymorphisms in Alzheimer's disease: a review
    Anália Nusya Medeiros Garcia
    Instituto de Ciencias Biologicas, UPE, Recife, Brazil
    J Mol Neurosci 39:342-5. 2009
    ..of cerebral cholesterol involves two mechanisms, dependent of apolipoprotein E and cholesterol 24-hydroxylase (CYP46)...
  69. ncbi Ontogenesis and regulation of cholesterol metabolism in the central nervous system of the mouse
    Gang Quan
    Department of Internal Medicine, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390 8887, USA
    Brain Res Dev Brain Res 146:87-98. 2003
    ..012 mg/day, and a reduction in the rate of cholesterol synthesis to 0.035 mg/day. Deletion of the NPC1 and CYP46A1 proteins markedly altered cholesterol metabolism in the CNS...
  70. ncbi Cholesterol loss enhances TrkB signaling in hippocampal neurons aging in vitro
    Mauricio G Martin
    VIB and Department of Human Genetics, Catholic University of Leuven, B 3000 Leuven, Belgium
    Mol Biol Cell 19:2101-12. 2008
    ....
  71. ncbi 24S-hydroxycholesterol: a marker of brain cholesterol metabolism
    D Lutjohann
    Department of Clinical Pharmacology, University of Bonn, Germany
    Pharmacopsychiatry 36:S102-6. 2003
    ..The enzyme mediating this conversion has been characterized at the molecular level (CYP46) and is mainly located in neurons...
  72. ncbi Meta-analysis of genetic variability in the beta-amyloid production, aggregation and degradation metabolic pathways and the risk of Alzheimer's disease
    J Llorca
    Division of Epidemiology and Computational Biology, University of Cantabria School of Medicine, Santander, Spain
    Acta Neurol Scand 117:1-14. 2008
    ..Variants in genes encoding enzymes involved in production, aggregation or degradation of beta-amyloid are potential risk factors for sporadic Alzheimer's disease (AD)...
  73. ncbi Cholesterol homeostasis and the pathophysiology of Alzheimer's disease
    Jean Francois Blain
    Douglas Hospital Research Centre, 6875 LaSalle Blvd, Verdun, Quebec, H4H 1R3, Canada
    Expert Rev Neurother 4:823-9. 2004
    ....
  74. ncbi Cholesterol-24S-hydroxylase (CYP46A1) is specifically expressed in neurons of the neural retina
    Lionel Bretillon
    Eye and Nutrition Research Group, UMR 1129 FLAVIC, INRA, ENESAD, University of Burgundy, Dijon, France, and Department of Laboratory Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden
    Curr Eye Res 32:361-6. 2007
    Increasing biological findings argue for the importance of cholesterol-24S-hydroxylase (CYP46A1) in cholesterol homeostasis in cerebral structures...
  75. ncbi Quantitation of two pathways for cholesterol excretion from the brain in normal mice and mice with neurodegeneration
    Chonglun Xie
    Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390 8887, USA
    J Lipid Res 44:1780-9. 2003
    ..The other probably involves the movement of cholesterol or one of its metabolites across the blood-brain barrier and may more closely mirror sterol turnover in pools such as glial cell membranes and myelin...
  76. ncbi Cyp46 (24S-cholesterol hydroxylase): a genetic risk factor for Alzheimer disease
    Benjamin Wolozin
    Arch Neurol 60:16-8. 2003
  77. ncbi Cholesterol-metabolizing cytochromes P450
    Irina A Pikuleva
    Department of Pharmacology and Toxicology, University of Texas, Medical Branch, 301 University Blvd, Galveston, TX 77555 1031, USA
    Drug Metab Dispos 34:513-20. 2006
    ..Finally, CYP46A1 is a brain-selective microsomal monooxygenase producing 24S-hydroxycholesterol from cholesterol...
  78. ncbi [Cholesterol and Alzheimer's disease]
    Janos Kalman
    Szegedi Tudomanyegyetem, Pszichiatriai Klinika, Alzheimer kór Kutatócsoport, Szeged
    Orv Hetil 146:1903-11. 2005
    ..On the other hand, the brain specific CYP46A1 enzyme is responsible for the degradation of cholesterol into a water soluble metabolite, called 24S-OH ..
  79. ncbi Association studies of cholesterol metabolism genes (CH25H, ABCA1 and CH24H) in Alzheimer's disease
    Nobuto Shibata
    Centre for Research in Neurodegenerative Diseases, Tanz Neuroscience Building, University of Toronto, 6 Queen s Park Crescent West, Toronto, Ont, Canada M5S 3H2
    Neurosci Lett 391:142-6. 2006
    ..ATP-binding cassette transporter A1 (ABCA1), cholesterol 25-hydroxylase (CH25H) and cholesterol 24-hydroxylase (CH24H). Case-control of North American Caucasians and AD families of Caribbean Hispanic origin were examined...
  80. ncbi 24S-hydroxycholesterol in cerebrospinal fluid is elevated in early stages of dementia
    A Papassotiropoulos
    Department of Psychiatry, University of Bonn, Sigmund Freud Strasse 25, 53105, Bonn, Germany
    J Psychiatr Res 36:27-32. 2002
    ..Conversion of cholesterol to 24S-hydroxycholesterol mediated by cholesterol 24S-hydroxylase (CYP46) is the major pathway for the elimination of brain cholesterol and the maintenance of brain cholesterol ..
  81. ncbi Transcriptional regulation of the human CYP46A1 brain-specific expression by Sp transcription factors
    Inês Milagre
    iMed Institute for Medicines and Research in Pharmaceutical Sciences, Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal
    J Neurochem 106:835-49. 2008
    ..The elimination of cholesterol from the brain involves its conversion into 24(S)-hydroxycholesterol by CYP46A1, and the efflux of this oxysterol across the blood-brain barrier...
  82. ncbi Variants of CYP46A1 may interact with age and APOE to influence CSF Abeta42 levels in Alzheimer's disease
    Annica Johansson
    Department of Clinical Neuroscience, Sahlgrenska University Hospital, Goteborg University, Goteborg, Sweden
    Hum Genet 114:581-7. 2004
    Recent studies have suggested that variants of CYP46A1, encoding cholesterol 24-hydroxylase (CYP46), confer risk for Alzheimer's disease (AD), a prospect substantiated by evidence of genetic association from several quantitative traits ..
  83. ncbi APOE promoter, ACE1 and CYP46 polymorphisms and beta-amyloid in Alzheimer's disease
    Katy A Chalmers
    University of Bristol, Department of Care of the Elderly, Frenchay Hospital, Bristol BS16 1LE, UK
    Neuroreport 15:95-8. 2004
    Polymorphisms in the APOE promoter, ACE1 and CYP46 genes have all been reported to be associated with Alzheimer's disease (AD)...
  84. ncbi Broad substrate specificity of human cytochrome P450 46A1 which initiates cholesterol degradation in the brain
    Natalia Mast
    Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, Texas 77555 1031, USA
    Biochemistry 42:14284-92. 2003
    The known activity of cytochrome P450 46A1 (P450 46A1) is 24(S)-hydroxylation of cholesterol...
  85. ncbi Exclusion of CYP46 and APOM as candidate genes for Alzheimer's disease in a French population
    Amro Kabbara
    Unité INSERM 508, Institut Pasteur de Lille, BP 245, 1 rue du Professeur Calmette, 59019 Lille Cedex, France
    Neurosci Lett 363:139-43. 2004
    ..With this background, we tested the potential association of the CYP46, APOM and APOF genes with the risk of developing AD...
  86. ncbi Cortical injury increases cholesterol 24S hydroxylase (Cyp46) levels in the rat brain
    CASANDRA M CARTAGENA
    Department of Neuroscience, Georgetown University Medical Center, Washington, D C 20057, USA
    J Neurotrauma 25:1087-98. 2008
    ..Here we investigated whether TBI altered the regulation of cholesterol 24S-hydroxylase (Cyp46), an enzyme that converts cholesterol to the more hydrophilic 24S-hydroxycholesterol...
  87. ncbi Biphasic requirement for geranylgeraniol in hippocampal long-term potentiation
    Tiina Kotti
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
    Proc Natl Acad Sci U S A 105:11394-9. 2008
    ..We conclude that geranylgeraniol acts specifically and quickly to affect LTP in the Schaffer collaterals of the hippocampus...
  88. ncbi Cytochrome P450 and gene activation--from pharmacology to cholesterol elimination and regression of atherosclerosis
    Pauli V Luoma
    Institute of Biomedicine, Pharmacology, University of Helsinki, Helsinki, Finland
    Eur J Clin Pharmacol 64:841-50. 2008
    ..Studies linking gene activation and the induction of cytochrome P450 with elevated plasma levels of apo AI and HDL-C and lowered plasma levels of LDL-C presented a new potential approach to prevent and treat atherosclerotic disease...
  89. ncbi CYP46A1 variants influence Alzheimer's disease risk and brain cholesterol metabolism
    Heike Kolsch
    Department of Psychiatry, University of Bonn, Germany
    Eur Psychiatry 24:183-90. 2009
    ..Only few gene variations in CYP46 gene (CYP46A1) have been investigated for their relevance as genetic risk factors of Alzheimer's disease (AD) and results are ..
  90. ncbi Lack of association of the cholesterol 24-hydroxylase (CYP46) intron 2 polymorphism with Alzheimer's disease
    Martin Ingelsson
    Harvard Medical School, Massachusetts General Hospital, 114 16th Street, Charlestown, MA 02129, USA
    Neurosci Lett 367:228-31. 2004
    ..An association was recently reported between an increased risk of Alzheimer's disease and an intron 2 AA genotype of CYP46, the enzyme hydroxylating cholesterol to 24S-hydroxycholesterol...
  91. ncbi Use of complementary cation and anion heavy-atom salt derivatives to solve the structure of cytochrome P450 46A1
    Mark Andrew White
    Sealy Center for Structural and Molecular Biophysics, UTMB Galveston, TX 77555, USA
    Acta Crystallogr D Biol Crystallogr 64:487-95. 2008
    Human cytochrome P450 46A1 (CYP46A1) is one of the key enzymes in cholesterol homeostasis in the brain...
  92. ncbi Lack of association between the CYP46 gene polymorphism and Italian late-onset sporadic Alzheimer's disease
    Andrea Tedde
    Department of Neurological and Psychiatric Sciences, University of Florence, Viale Pieraccini, 6 50139 Florence, Italy
    Neurobiol Aging 27:773.e1-773.e3. 2006
    ..We analyzed an intronic T-->C substitution (rs 754203) of the cholesterol 24S-hydroxylase (CYP46) gene, encoding an enzyme acting on brain cholesterol turnover, which has been recently associated with an ..
  93. ncbi The effects of gender and CYP46 and apo E polymorphism on 24S-hydroxycholesterol levels in Alzheimer's patients treated with statins
    Gloria Lena Vega
    Department of Clinical Nutrition, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9052, USA
    Curr Alzheimer Res 1:71-7. 2004
    To examine the effect of gender and polymorphisms of CYP46 and apo E on plasma levels of 24S-hydroxycholesterol in Alzheimer's disease (AD) patients and to determine whether these factors contribute to the variability in responses to ..
  94. ncbi A cluster of cholesterol-related genes confers susceptibility for Alzheimer's disease
    Andreas Papassotiropoulos
    Division of Psychiatry Research, University of Zurich, Zurich, Switzerland
    J Clin Psychiatry 66:940-7. 2005
    ..Polygenic diseases are related to the complex interplay of genetic variations. We evaluated whether clusters of cholesterol- and lipid-related genetic variations are associated with Alzheimer's disease...
  95. ncbi CYP46 T/C polymorphism is not associated with Alzheimer's dementia in a population from Hungary
    Anna Juhász
    Department of Psychiatry, Albert Szent Gyorgyi Medical and Pharmaceutical Center, Faculty of Medicine, University of Szeged, Szeged, Hungary
    Neurochem Res 30:943-8. 2005
    ..1, where a gene encoding a cholesterol degrading enzyme of the brain, called 24-hydroxylase (CYP46A1) is located, has been linked with AD...
  96. ncbi Transcriptional regulation of cholesterol 24-hydroxylase by histone deacetylase inhibitors
    Marjan Shafaati
    Department of Laboratory Medicine, Division of Clinical Chemistry, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden
    Biochem Biophys Res Commun 378:689-94. 2009
    ..if epigenetic mechanisms are involved in the regulation of the brain-specific enzyme cholesterol 24-hydroxylase (CYP46A1), a key regulator of brain cholesterol elimination...
  97. ncbi On the turnover of brain cholesterol in patients with Alzheimer's disease. Abnormal induction of the cholesterol-catabolic enzyme CYP46 in glial cells
    N Bogdanovic
    Division of Geriatric Medicine, Karolinska Institutet, Huddinge University Hospital, Huddinge, Sweden
    Neurosci Lett 314:45-8. 2001
    ..the brain, involving conversion of brain cholesterol into 24S-hydroxycholesterol by the neuronal oxidative enzyme CYP46. There was a marked difference in the distribution of CYP46 in brains of control and AD patients...
  98. ncbi Oxysterol biosynthetic enzymes
    D W Russell
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75235 9046, USA
    Biochim Biophys Acta 1529:126-35. 2000
    ..This article focuses on the properties of these enzymes...
  99. ncbi Association of blood pressure and genetic background with white matter lesions in patients with mild cognitive impairment
    Samantha Galluzzi
    LENITEM Laboratory of Epidemiology, Neuroimaging and Telemedicine, IRCCS Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy
    J Gerontol A Biol Sci Med Sci 63:510-7. 2008
    ..Polymorphisms of cystatin C (CST3) and cholesterol 24-hydroxylase (CYP46) genes, putative risk factors for cerebrovascular disease, were determined. Results...
  100. ncbi Genetic variation in the cholesterol 24-hydroxylase (CYP46) gene and the risk of Alzheimer's disease
    Purnima Desai
    Department of Human Genetics, University of Pittsburgh, 130 DeSoto Street, Pittsburgh, PA 15216, USA
    Neurosci Lett 328:9-12. 2002
    ..Increasing evidence points to a link between brain cholesterol turnover and AD. The CYP46 gene encodes for the enzyme, cholesterol 24-hydroxylase, which plays a key role in brain cholesterol turnover...
  101. ncbi [Correlation of cholesterol 24-hydroxylase and ATP-binding cassette transporter A1 polymorphisms with Alzheimer's disease]
    Fen Wang
    Department of Neurology, Xuanwu Hospital of Capital University of Medical Sciences, Beijing 100053, China
    Zhonghua Yi Xue Za Zhi 87:614-8. 2007
    ..the association of the single nucleotide polymorphisms (SNPs) A-->G in the intron 2 of cholesterol 24-hydroxylase (CYP46) gene and G-->A (R219K) in the exon 6 of ATP-binding cassette transporter A1 (ABCA1) gene with sporadic Alzheimer'..

Research Grants59

  1. Cholesterol metabolizing P450s: structure and function
    Irina Pikuleva; Fiscal Year: 2009
    ..degradation, bile acid biosynthesis is initiated and controlled by cytochrome P450 7A1 (CYP7A1), in the brain by CYP46A1, and in most extrahepatic tissues by CYP27A1. Steroid hormone biosynthesis is initiated by CYP11A1...
  2. Cholesterol metabolizing P450s: structure and function
    Irina Pikuleva; Fiscal Year: 2009
    ..degradation, bile acid biosynthesis is initiated and controlled by cytochrome P450 7A1 (CYP7A1), in the brain by CYP46A1, and in most extrahepatic tissues by CYP27A1. Steroid hormone biosynthesis is initiated by CYP11A1...
  3. Cholesterol metabolizing P450s: structure and function
    Irina A Pikuleva; Fiscal Year: 2010
    ..degradation, bile acid biosynthesis is initiated and controlled by cytochrome P450 7A1 (CYP7A1), in the brain by CYP46A1, and in most extrahepatic tissues by CYP27A1. Steroid hormone biosynthesis is initiated by CYP11A1...
  4. Significance of CYP46A1 and other P450s in retinal function
    Irina Pikuleva; Fiscal Year: 2009
    ..CYP27A1 is a polyfunctional ubiquitous sterol 27-hydroxylase extensively characterized by us and others. CYP46A1 is a recently cloned and therefore much less studied enzyme. We began to work with CYP46A1 only four years ago...
  5. Significance of CYP46A1 and other P450s in retinal function
    Irina A Pikuleva; Fiscal Year: 2010
    ..CYP27A1 is a polyfunctional ubiquitous sterol 27-hydroxylase extensively characterized by us and others. CYP46A1 is a recently cloned and therefore much less studied enzyme. We began to work with CYP46A1 only four years ago...
  6. Significance of CYP46A1 and other P450s in retinal function
    Irina Pikuleva; Fiscal Year: 2009
    ..CYP27A1 is a polyfunctional ubiquitous sterol 27-hydroxylase extensively characterized by us and others. CYP46A1 is a recently cloned and therefore much less studied enzyme. We began to work with CYP46A1 only four years ago...
  7. Cholesterol and Sphingolipid Metabolism in Alzheimer's Disease
    Ta Yuan Chang; Fiscal Year: 2010
    ..We enlist three specific aims: Specific Aim 1: To test the effect of inactivating the enzyme 24(S)-hydroxylase CYP46A1, on Acat1-/- (A1-) mediated modulations on hAPP, HMGR and ABCA1 in AD mice neurons...
  8. Fatty Acid Synthesis in Specific Hypothalamic Neurons: Control of Appetite and En
    Joseph Goldstein; Fiscal Year: 2007
    ..This interdisciplinary approach is possible only through support of this Program Project Grant. ..
  9. Cyp46 regulation of cholesterol efflux and ABeta
    CASANDRA CARTAGENA; Fiscal Year: 2007
    ..The study will determine whether increasing expression of brain specific CYP46 will alter Abeta levels...
  10. Biomarkers in Aging, MCI and Alzheimer's Disease
    Douglas Galasko; Fiscal Year: 2007
    ..MCI, mild AD), degree of cognitive impairment, and genetic risk factors for AD (apolipoprotein E [ApoE] and CYP46 genotypes) will be examined, and the extent of change in biomarkers over 12 months will be analyzed...
  11. Enzymes of Skin Lipid Metabolism
    David Russell; Fiscal Year: 2009
    ..The research is relevant to skin disease, dry eye syndrome, and cholesterol metabolism. ..
  12. Nuclear hormone receptor regulation of cholesterol absorption
    Joyce J Repa; Fiscal Year: 2010
    ..Additional mechanisms to reduce the cholesterol transport protein, NPC1L1, particularly in an intestine-specific manner, may result in the development of safer drugs for the treatment of hypercholesterolemia and cholelithiasis. ..
  13. Nuclear hormone receptor regulation of cholesterol absorption
    Joyce Repa; Fiscal Year: 2009
    ..Additional mechanisms to reduce the cholesterol transport protein, NPC1L1, particularly in an intestine-specific manner, may result in the development of safer drugs for the treatment of hypercholesterolemia and cholelithiasis. ..
  14. Nuclear hormone receptor regulation of cholesterol absorption
    Joyce J Repa; Fiscal Year: 2010
    ..Additional mechanisms to reduce the cholesterol transport protein, NPC1L1, particularly in an intestine-specific manner, may result in the development of safer drugs for the treatment of hypercholesterolemia and cholelithiasis. ..
  15. Induction of breast cancer in MMTVneu mice
    William Baldwin; Fiscal Year: 2002
    ..Overall, the purpose of this study is to examine 4-nonylphenol's effects on breast cancer growth and its mechanism of action on the mammary tumor. ..
  16. ENDOCRINE ROLES OF STEROID 5 ALPHA REDUCTASE ISOZYMES
    David Russell; Fiscal Year: 2003
    ....
  17. Function and Signaling Mechanisms of Leptin Receptors
    Joyce Repa; Fiscal Year: 2005
    ..A better understanding of the signal transduction pathway used by leptin may reveal novel strategies to enhance or inhibit leptin's biological activities for therapeutic purposes. ..
  18. Cholesterol-metabolizing P450s and Alzheimer's disease
    Irina Pikuleva; Fiscal Year: 2007
    ..If funded, the release time and salary support will significantly enhance the P.I.'s career in basic science research and make it more medically oriented. ..
  19. Significance of CYP46A1 and other P450s in retinal function
    Irina Pikuleva; Fiscal Year: 2007
    ..CYP27A1 is a polyfunctional ubiquitous sterol 27-hydroxylase extensively characterized by us and others. CYP46A1 is a recently cloned and therefore much less studied enzyme. We began to work with CYP46A1 only four years ago...