Abstract
Liver X receptors (LXRα and LXRβ ) are oxysterol receptors that function as master transcription factors mediating cholesterol homeostasis in the periphery. LXRs regulate the levels of the ABCA1 and ABCG1 cholesterol transporters as well as apolipoproteins (apoE and apoC) in various cells thereby affecting cholesterol transport and metabolism. In the brain, LXRs regulate ABCA1 in both neurons and glia resulting in cholesterol efflux from these cells. In addition, the expression of apolipoprotein E (apoE), synthesized primarily by astrocytes and microglia, is also upregulated by LXR agonists. As both apoE and the ABCA1 transporter are intimately involved in amyloid-β peptide (Aβ ) transport and clearance, activation of these genes by LXR agonists in brain may have a significant impact on Aβ deposition and amyloid/ neuritic plaque formation. Furthermore, LXR activation has been shown to have significant anti-inflammatory properties. Taken together, these findings suggest that brain-penetrable LXR agonists or modulators may be useful therapeutic agents for the treatment and (or) prevention of Alzheimers disease.
Keywords: Nuclear hormone receptors, cholesterol, amyloid, ABCA1, apolipoprotein E, glia
Current Alzheimer Research
Title: Liver X Receptor-Mediated Gene Regulation and Cholesterol Homeostasis in Brain: Relevance to Alzheimers Disease Therapeutics
Volume: 4 Issue: 2
Author(s): Guoqing Cao, Kelly R. Bales, Ronald B. DeMattos and Steven M. Paul
Affiliation:
Keywords: Nuclear hormone receptors, cholesterol, amyloid, ABCA1, apolipoprotein E, glia
Abstract: Liver X receptors (LXRα and LXRβ ) are oxysterol receptors that function as master transcription factors mediating cholesterol homeostasis in the periphery. LXRs regulate the levels of the ABCA1 and ABCG1 cholesterol transporters as well as apolipoproteins (apoE and apoC) in various cells thereby affecting cholesterol transport and metabolism. In the brain, LXRs regulate ABCA1 in both neurons and glia resulting in cholesterol efflux from these cells. In addition, the expression of apolipoprotein E (apoE), synthesized primarily by astrocytes and microglia, is also upregulated by LXR agonists. As both apoE and the ABCA1 transporter are intimately involved in amyloid-β peptide (Aβ ) transport and clearance, activation of these genes by LXR agonists in brain may have a significant impact on Aβ deposition and amyloid/ neuritic plaque formation. Furthermore, LXR activation has been shown to have significant anti-inflammatory properties. Taken together, these findings suggest that brain-penetrable LXR agonists or modulators may be useful therapeutic agents for the treatment and (or) prevention of Alzheimers disease.
Export Options
About this article
Cite this article as:
Cao Guoqing, Bales R. Kelly, DeMattos B. Ronald and Paul M. Steven, Liver X Receptor-Mediated Gene Regulation and Cholesterol Homeostasis in Brain: Relevance to Alzheimers Disease Therapeutics, Current Alzheimer Research 2007; 4 (2) . https://dx.doi.org/10.2174/156720507780362173
DOI https://dx.doi.org/10.2174/156720507780362173 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
Call for Papers in Thematic Issues
New Advances in the Prevention, Diagnosis, Treatment, and Rehabilitation of Alzheimer's Disease
Aims and Scope: Introduction: Alzheimer's disease (AD) poses a significant global health challenge, with an increasing prevalence that demands concerted efforts to advance our understanding and strategies for prevention, diagnosis, treatment, and rehabilitation. This thematic issue aims to bring together cutting-edge research and innovative approaches from multidisciplinary perspectives to address ...read more
Current updates on the Role of Neuroinflammation in Neurodegenerative Disorders
Neuroinflammation is an invariable hallmark of chronic and acute neurodegenerative disorders and has long been considered a potential drug target for Alzheimer?s disease (AD) and dementia. Significant evidence of inflammatory processes as a feature of AD is provided by the presence of inflammatory markers in plasma, CSF and postmortem brain ...read more
Deep Learning for Advancing Alzheimer's Disease Research
Alzheimer's disease (AD) poses a significant global health challenge, with an increasing number of individuals affected yearly. Deep learning, a subfield of artificial intelligence, has shown immense potential in various domains, including healthcare. This thematic issue of Current Alzheimer Research explores the application of deep learning techniques in advancing our ...read more
Diagnostic and therapeutic biomarkers of dementia
Dementia affects 18 million people worldwide. Dementia is a syndrome of symptoms caused by brain disease, usually chronic or progressive, clinically characterized by multiple impairments of higher cortical functions such as memory, thinking, orientation, and learning. In addition, in the course of dementia, cognitive deficits are observed, which often hinder ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
The Canadian Biomarker Integration Network in Depression (CAN-BIND): Advances in Response Prediction
Current Pharmaceutical Design COVID-19-associated Coagulopathy and Thromboembolism: Determination of Their Patterns and Risk Factors as Predictors of Mortality Among Severe COVID-19 Patients
Current Vascular Pharmacology Development of Phthalimide-Donepezil Hybrids as Potent Multitarget- Directed Ligands for the Treatment of Alzheimer’s Disease
Letters in Drug Design & Discovery Cardiovascular Complications of Sleep Disorders: A Better Night’s Sleep for a Healthier Heart / From Bench to Bedside
Current Vascular Pharmacology <i>Lactobacillus Rhamnosus</i> UBLR-58 and Diclofenac Potentiate the Anti- Alzheimer Activity of Curcumin in Mice
Current Enzyme Inhibition QSAR and Molecular Docking Techniques for the Discovery of Potent Monoamine Oxidase B Inhibitors: Computer-Aided Generation of New Rasagiline Bioisosteres
Current Topics in Medicinal Chemistry Integration of <sup>18</sup>FDG-PET Metabolic and Functional Connectomes in the Early Diagnosis and Prognosis of the Alzheimer's Disease
Current Alzheimer Research Responses of Glial Cells to Stress and Glucocorticoids
Current Immunology Reviews (Discontinued) Flavonoids in Neurodegeneration: Limitations and Strategies to Cross CNS Barriers
Current Medicinal Chemistry Newer Insights in Personalized and Evidence Based Medicine- the Role of MicroRNAs
Current Pharmacogenomics and Personalized Medicine Applicability and Approaches of (Meth) Acrylate Copolymers (Eudragits) in Novel Drug Delivery Systems
Current Drug Therapy Clinical Significance of Cytokines and Chemokines in Neuropsychiatric Systemic Lupus Erythematosus
Current Rheumatology Reviews An Update on Drug Interactions with the Herbal Medicine Ginkgo biloba
Current Drug Metabolism Protein Aggregation in Neurodegenerative Diseases: Insights from Computational Analyses
Current Bioinformatics Novel Multitarget Hybrid Compounds for the Treatment of Alzheimer’s Disease
Current Topics in Medicinal Chemistry Brain local and regional neuroglial alterations in Alzheimer´s Disease: cell types, responses and implications.
Current Alzheimer Research Interactions of VDAC with Proteins Involved in Neurodegenerative Aggregation: An Opportunity for Advancement on Therapeutic Molecules
Current Medicinal Chemistry Adult Stem Cell Transplantation in Stroke: Its Limitations and Prospects
Current Stem Cell Research & Therapy Quinoline: An Attractive Scaffold in Drug Design
Mini-Reviews in Medicinal Chemistry The Neuropharmacology of Cluster Headache and other Trigeminal Autonomic Cephalalgias
Current Neuropharmacology