Paper Search Console

Home Search Page About Contact

Journal Title

Title of Journal: Mol Neurobiol

Search In Journal Title:

Abbravation: Molecular Neurobiology

Search In Journal Abbravation:

Publisher

Springer US

Search In Publisher:

DOI

10.1002/ctpp.2150300108

Search In DOI:

ISSN

1559-1182

Search In ISSN:
Search In Title Of Papers:

Cholesterol 24SHydroxylase Overexpression Inhibit

Authors: Miguel Moutinho Maria João Nunes Anita Q Gomes Maria João Gama Angel CedazoMinguez Cecília M P Rodrigues Ingemar Björkhem Elsa Rodrigues
Publish Date: 2014/08/02
Volume: 51, Issue: 3, Pages: 1489-1503
PDF Link

Abstract

The neuronalspecific cholesterol 24Shydroxylase CYP46A1 is important for brain cholesterol elimination Cyp46a1 null mice exhibit severe deficiencies in learning and hippocampal longterm potentiation suggested to be caused by a decrease in isoprenoid intermediates of the mevalonate pathway Conversely transgenic mice overexpressing CYP46A1 show an improved cognitive function These results raised the question of whether CYP46A1 expression can modulate the activity of proteins that are crucial for neuronal function namely of isoprenylated small guanosine triphosphatebinding proteins sGTPases Our results show that CYP46A1 overexpression in SHSY5Y neuroblastoma cells and in primary cultures of rat cortical neurons leads to an increase in 3hydroxy3methylglutarylCoA reductase activity and to an overall increase in membrane levels of RhoA Rac1 Cdc42 and Rab8 This increase is accompanied by a specific increase in RhoA activation Interestingly treatment with lovastatin or a geranylgeranyltransferaseI inhibitor abolished the CYP46A1 effect The CYP46A1mediated increase in sGTPases membrane abundance was confirmed in vivo in membrane fractions obtained from transgenic mice overexpressing this enzyme Moreover CYP46A1 overexpression leads to a decrease in the liver X receptor LXR transcriptional activity and in the mRNA levels of ATPbinding cassette transporter 1 subfamily A member 1 and apolipoprotein E This effect was abolished by inhibition of prenylation or by cotransfection of a RhoA dominantnegative mutant Our results suggest a novel regulatory axis in neurons under conditions of membrane cholesterol reduction by increased CYP46A1 expression neurons increase isoprenoid synthesis and sGTPase prenylation This leads to a reduction in LXR activity and consequently to a decrease in the expression of LXR target genesWe deeply thank Dr Peter Tontonoz Howard Hughes Medical Institute University of California Los Angeles USA for kindly providing the LXRE and LXRE mutABCA1 luciferase reporter plasmids and to Dr Peter Jordan Instituto Nacional de Saúde Doutor Ricardo Jorge Lisbon Portugal for the plasmid encoding a dominant negative mutant of RhoA pEGFP RhoA N19 This work was supported by FEDER COMPETE Programme and by national funds ER FCT—Fundação para a Ciência e a Tecnologia—project PTDC/SAUNMC/110809/2009 and PhD grants SFRH/BD/41848/2007 to MJN and SFRH/BD/78041/2011 to MM and by the Swedish Science Council and Swedish Brain Power IB


Keywords:

References


.
Search In Abstract Of Papers:
Other Papers In This Journal:

  1. Combination of HBO and Memantine in Focal Cerebral Ischemia: Is There a Synergistic Effect?
  2. VEGF-A 165 Potently Induces Human Blood–Nerve Barrier Endothelial Cell Proliferation, Angiogenesis, and Wound Healing In Vitro
  3. Sigma-1 Receptor Modulates Neuroinflammation After Traumatic Brain Injury
  4. PGE 2 Inhibits IL-10 Production via EP2-Mediated β-Arrestin Signaling in Neuroinflammatory Condition
  5. Age and Sex Dependent Alteration in Presenilin Expression in Mouse Cerebral Cortex
  6. Determining the Roles of Inositol Trisphosphate Receptors in Neurodegeneration: Interdisciplinary Perspectives on a Complex Topic
  7. Anxiolytic Actions of Motilin in the Basolateral Amygdala
  8. Mdivi-1 Protects Against Ischemic Brain Injury via Elevating Extracellular Adenosine in a cAMP/CREB-CD39-Dependent Manner
  9. MicroRNA Expression Signatures Determine Prognosis and Survival in Glioblastoma Multiforme—a Systematic Overview
  10. Tetramethylpyrazine Promotes Migration of Neural Precursor Cells via Activating the Phosphatidylinositol 3-Kinase Pathway
  11. Anti-amyloid Aggregation Activity of Natural Compounds: Implications for Alzheimer’s Drug Discovery
  12. TYROBP in Alzheimer’s Disease
  13. Shengmai Formula Ameliorates Pathological Characteristics in AD C. elegans
  14. New Molecular Insights into Cellular Survival and Stress Responses: Neuroprotective Role of Cellular Prion Protein (PrP C )
  15. Adoptive Autophagy Activation: a Much-Needed Remedy Against Chemical Induced Neurotoxicity/Developmental Neurotoxicity
  16. Plasma miR-221/222 Family as Novel Descriptive and Prognostic Biomarkers for Glioma
  17. Critical Roles of Voltage-Dependent Sodium Channels in the Process of Synaptogenesis During the Postnatal Cortical Development of Rats
  18. A Nonrewarding NMDA Receptor Antagonist Impairs the Acquisition, Consolidation, and Expression of Morphine Conditioned Place Preference in Mice
  19. DAPK1 Signaling Pathways in Stroke: from Mechanisms to Therapies
  20. Dissecting the Inter-Substrate Navigation of Migrating Glioblastoma Cells with the Stripe Assay Reveals a Causative Role of ROCK
  21. Ketamine Inhibits ATP-Evoked Exocytotic Release of Brain-Derived Neurotrophic Factor from Vesicles in Cultured Rat Astrocytes
  22. Rapamycin Effectively Impedes Melamine-Induced Impairments of Cognition and Synaptic Plasticity in Wistar Rats
  23. Il1-β Involvement in Cognitive Impairment after Sepsis
  24. Gastrin-Releasing Peptide Receptor Knockdown Induces Senescence in Glioblastoma Cells
  25. Role of Rho Kinase Inhibition in the Protective Effect of Fasudil and Simvastatin Against 3-Nitropropionic Acid-Induced Striatal Neurodegeneration and Mitochondrial Dysfunction in Rats
  26. Feedback Regulation of SREBP and Aromatase in A β(25-35)-Supplemented Human Neuroblastoma Cells
  27. Reversal of Beta-Amyloid-Induced Neurotoxicity in PC12 Cells by Curcumin, the Important Role of ROS-Mediated Signaling and ERK Pathway
  28. A Novel Bioresorbable Device as a Controlled Release System for Protecting Cells from Oxidative Stress from Alzheimer’s Disease
  29. Bradykinin Postconditioning Protects Pyramidal CA1 Neurons Against Delayed Neuronal Death in Rat Hippocampus
  30. Olfactory Ensheathing Cell-Conditioned Medium Reverts Aβ 25–35 -Induced Oxidative Damage in SH-SY5Y Cells by Modulating the Mitochondria-Mediated Apoptotic Pathway
  31. C5a/C5aR Pathway Plays a Vital Role in Brain Inflammatory Injury via Initiating Fgl-2 in Intracerebral Hemorrhage
  32. Deferoxamine Preconditioning of Neural-Like Cells Derived from Human Wharton’s Jelly Mesenchymal Stem Cells as a Strategy to Promote Their Tolerance and Therapeutic Potential: An In Vitro Study
  33. Downregulation of the Long Non-Coding RNA Meg3 Promotes Angiogenesis After Ischemic Brain Injury by Activating Notch Signaling
  34. Bisphenol A Represses Dopaminergic Neuron Differentiation from Human Embryonic Stem Cells through Downregulating the Expression of Insulin-like Growth Factor 1
  35. Melatonin Inhibits Manganese-Induced Motor Dysfunction and Neuronal Loss in Mice: Involvement of Oxidative Stress and Dopaminergic Neurodegeneration
  36. Introduction to Extracellular Vesicles: Biogenesis, RNA Cargo Selection, Content, Release, and Uptake
  37. Up-Regulation of Glis2 Involves in Neuronal Apoptosis After Intracerebral Hemorrhage in Adult Rats
  38. Differentiation of Human Endometrial Stem Cells into Schwann Cells in Fibrin Hydrogel as 3D Culture
  39. Development of the New Group of Indole-Derived Neuroprotective Drugs Affecting Oxidative Stress
  40. The Distinct Role of ADAM17 in APP Proteolysis and Microglial Activation Related to Alzheimer’s Disease
  41. Dopamine Burden Triggers Neurodegeneration via Production and Release of TNF-α from Astrocytes in Minimal Hepatic Encephalopathy
  42. Altered mRNA Levels of Glucocorticoid Receptor, Mineralocorticoid Receptor, and Co-Chaperones (FKBP5 and PTGES3) in the Middle Frontal Gyrus of Autism Spectrum Disorder Subjects
  43. Piperine Reverses Chronic Unpredictable Mild Stress-Induced Behavioral and Biochemical Alterations in Rats
  44. Neuroimaging Results Impose New Views on Alzheimer’s Disease—the Role of Amyloid Revised
  45. Modulation of Diabetes-Induced Oxidative Stress, Apoptosis, and Ca 2+ Entry Through TRPM2 and TRPV1 Channels in Dorsal Root Ganglion and Hippocampus of Diabetic Rats by Melatonin and Selenium
  46. Regulation of Sirtuin 3-Mediated Deacetylation of Cyclophilin D Attenuated Cognitive Dysfunction Induced by Sepsis-Associated Encephalopathy in Mice
  47. The Cdk5 Kinase Downregulates ATP-Gated Ionotropic P2X 3 Receptor Function Via Serine Phosphorylation
  48. Liver X Receptor β Is Involved in Formalin-Induced Spontaneous Pain
  49. Persistent mitoK ATP Activation Is Involved in the Isoflurane-induced Cytotoxicity
  50. Immunohistochemical Study of Postnatal Neurogenesis After Whole-body Exposure to Electromagnetic Fields: Evaluation of Age- and Dose-Related Changes in Rats
  51. Identification of Endophilins 1 and 3 as Selective Binding Partners for VGLUT1 and Their Co-Localization in Neocortical Glutamatergic Synapses: Implications for Vesicular Glutamate Transporter Trafficking and Excitatory Vesicle Formation
  52. Protective Effects of UCF-101 on Cerebral Ischemia–Reperfusion (CIR) is Depended on the MAPK/p38/ERK Signaling Pathway
  53. Epigenetic Regulation of SNAP25 Prevents Progressive Glutamate Excitotoxicty in Hypoxic CA3 Neurons
  54. Electroacupuncture Attenuates Reference Memory Impairment Associated with Astrocytic NDRG2 Suppression in APP/PS1 Transgenic Mice
  55. Systematic Genetic Analysis of the SMPD1 Gene in Chinese Patients with Parkinson’s Disease
  56. The Effects of Volatile Anesthetics on the Extracellular Accumulation of [ 3 H]GABA in Rat Brain Cortical Slices
  57. Neurological Damage in MSUD: The Role of Oxidative Stress
  58. Elevated S100B and Neuron Specific Enolase Levels in Patients with Migraine-without Aura: Evidence for Neurodegeneration?
  59. High Plasma Levels of d -Dimer Are Independently Associated with a Heightened Risk of Deep Vein Thrombosis in Patients with Intracerebral Hemorrhage
  60. Perforin Promotes Amyloid Beta Internalisation in Neurons
  61. Investigation of Long Non-coding RNA Expression Profiles in the Substantia Nigra of Parkinson’s Disease
  62. Cellular Neoplastic Transformation Induced by 916 MHz Microwave Radiation
  63. Effects of the Chinese Traditional Prescription Xiaoyaosan Decoction on Chronic Immobilization Stress-induced Changes in Behavior and Brain BDNF, TrkB, and NT-3 in Rats
  64. Serotonin and Prefrontal Cortex Function: Neurons, Networks, and Circuits
  65. Alterations Induced by Ischemic Preconditioning on Secretory Pathways Ca 2+ -ATPase (SPCA) Gene Expression and Oxidative Damage After Global Cerebral Ischemia/Reperfusion in Rats
  66. Sequences of the Non-Coding RNA, NTAB, are Contained within the 3′-UTR of Human and Rat EAAT2/GLT-1 Transcripts and Act as Transcriptional Enhancers
  67. Effects of Agomelatine on Oxidative Stress in the Brain of Mice After Chemically Induced Seizures
  68. Primary Skin Fibroblasts as a Model of Parkinson's Disease
  69. Bergmann Glia, Long-Term Depression, and Autism Spectrum Disorder
  70. Modulation of Notch Signaling Pathway to Prevent H 2 O 2 /Menadione-Induced SK-N-MC Cells Death by EUK134
  71. LINGO-1-Fc-Transduced Neural Stem Cells Are Effective Therapy for Chronic Stage Experimental Autoimmune Encephalomyelitis
  72. Cofilin Inhibition Restores Neuronal Cell Death in Oxygen–Glucose Deprivation Model of Ischemia

Search Result: