Abstract
Oxysterols are a family of 27-carbon cholesterol oxidation derivatives that may be absorbed with the diet or originated endogenously. These cholesterol metabolites are now considered to be potentially involved in the initiation and progression of major chronic diseases including atherosclerosis, neurodegenerative processes, diabetes, kidney failure, and ethanol intoxication. Thus we deemed it of interest to comprehensively analyze the actual relevance of oxysterols, acting through up-regulation of inflammation, apoptosis and fibrosis, to human pathology from cell signaling to disease expression; we also review the available literature on related therapeutic prospects. Oxysterols of pathophysiologic relevance generally possess a strong pro-oxidant effect, chiefly since they activate NAD(P)H oxidases. Further, stimulation of the MEK/ERK signaling pathway appears to be a common feature of the biochemical effects of this class of compounds. Selective metabolic inhibitors of NAD(P)H oxidase and the MAPK pathway might quench or even prevent the cytotoxic effects of pathological accumulation of cholesterol oxides in cells and tissues. The marked reduction of plasma oxysterols reported for statin-based therapy is interesting: it has been associated with a lower incidence and prevalence of Alzheimers disease (AD) and vascular dementia. Quenching reactive oxygen species generation seems the likely mechanism exploited by statins against AD incidence and development; intervention with antioxidants might thus also be reconsidered as regards molecular “integrated” prevention and possible therapy of human “multifactorial” disease processes.
Keywords: Cholesterol, oxysterols, lipid metabolism, apoptosis, inflammation, statins, antioxidants
Current Medicinal Chemistry
Title: Cholesterol Oxidation Products and Disease: An Emerging Topic of Interest in Medicinal Chemistry
Volume: 16 Issue: 6
Author(s): Barbara Sottero, Paola Gamba, Simona Gargiulo, Gabriella Leonarduzzi and Giuseppe Poli
Affiliation:
Keywords: Cholesterol, oxysterols, lipid metabolism, apoptosis, inflammation, statins, antioxidants
Abstract: Oxysterols are a family of 27-carbon cholesterol oxidation derivatives that may be absorbed with the diet or originated endogenously. These cholesterol metabolites are now considered to be potentially involved in the initiation and progression of major chronic diseases including atherosclerosis, neurodegenerative processes, diabetes, kidney failure, and ethanol intoxication. Thus we deemed it of interest to comprehensively analyze the actual relevance of oxysterols, acting through up-regulation of inflammation, apoptosis and fibrosis, to human pathology from cell signaling to disease expression; we also review the available literature on related therapeutic prospects. Oxysterols of pathophysiologic relevance generally possess a strong pro-oxidant effect, chiefly since they activate NAD(P)H oxidases. Further, stimulation of the MEK/ERK signaling pathway appears to be a common feature of the biochemical effects of this class of compounds. Selective metabolic inhibitors of NAD(P)H oxidase and the MAPK pathway might quench or even prevent the cytotoxic effects of pathological accumulation of cholesterol oxides in cells and tissues. The marked reduction of plasma oxysterols reported for statin-based therapy is interesting: it has been associated with a lower incidence and prevalence of Alzheimers disease (AD) and vascular dementia. Quenching reactive oxygen species generation seems the likely mechanism exploited by statins against AD incidence and development; intervention with antioxidants might thus also be reconsidered as regards molecular “integrated” prevention and possible therapy of human “multifactorial” disease processes.
Export Options
About this article
Cite this article as:
Sottero Barbara, Gamba Paola, Gargiulo Simona, Leonarduzzi Gabriella and Poli Giuseppe, Cholesterol Oxidation Products and Disease: An Emerging Topic of Interest in Medicinal Chemistry, Current Medicinal Chemistry 2009; 16 (6) . https://dx.doi.org/10.2174/092986709787458353
DOI https://dx.doi.org/10.2174/092986709787458353 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...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
-
Fine Tuning of Intracellular Ca<sup>2+</sup> Content by Pharmacological Agents – A Strategy to Prevent Synapse Loss in Alzheimer Disease Hippocampal Neurons
Current Alzheimer Research VIP in Neurological Diseases: More Than A Neuropeptide
Endocrine, Metabolic & Immune Disorders - Drug Targets Neuroprotective Effects of Citrus reticulata in Scopolamine-Induced Dementia Oxidative Stress in Rats
CNS & Neurological Disorders - Drug Targets Common Genetic Conditions of Ischemic Stroke to Keep in Mind
Current Molecular Medicine The Breath of Life: Recent Patents on Placental and Amnion Derived Cells for Treatment of Bronchopulmonary Dysplasia
Recent Patents on Regenerative Medicine The Involvement of Post-Translational Modifications in Alzheimer's Disease
Current Alzheimer Research Cognitive Improvement by Activation of α7 Nicotinic Acetylcholine Receptors: From Animal Models to Human Pathophysiology
Current Pharmaceutical Design Homocysteine Enhances Transmigration of Rat Monocytes through a Brain Capillary Endothelial Cell Monolayer via ICAM-1
Current Neurovascular Research Potential Roles of MyomiRs in Cardiac Development and Related Diseases
Current Cardiology Reviews Differentiating Normal from Pathological Brain Ageing Using Standard Neuropsychological Tests
Current Alzheimer Research Primary Antiphospholipid Syndrome and Pulmonary Hypertension
Current Pharmaceutical Design Thiamine and Alcohol for Brain Pathology: Super-imposing or Different Causative Factors for Brain Damage?
Current Drug Abuse Reviews Metabolic Profiling in Multiple Sclerosis and Other Disorders by Quantitative Analysis of Cerebrospinal Fluid Using Nuclear Magnetic Resonance Spectroscopy
Current Pharmaceutical Biotechnology A Novel Nanoformulation of Ellagic Acid is Promising in Restoring Oxidative Homeostasis in Rat Brains with Alzheimer’s Disease
Current Drug Metabolism Human Use of Leucoselect® Phytosome® with Special Reference to Inflammatory- Allergic Pathologies in Frail Elderly Patients
Current Pharmaceutical Design Brain local and regional neuroglial alterations in Alzheimer´s Disease: cell types, responses and implications.
Current Alzheimer Research Management of Dyslipidaemia for the Prevention of Stroke: Clinical Practice Recommendations from the Lipid Association of India
Current Vascular Pharmacology Current Understanding of Dietary Polyphenols and their Role in Health and Disease
Current Nutrition & Food Science Micronutrient Biofortification in Rice through New Breeding Techniques (NBTs): Bangladesh Perspective
Current Nutraceuticals Calpains as a Target for Therapy of Neurodegenerative Diseases: Putative Role of Lithium
Current Drug Metabolism