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
-
Rationale for Peptide and DNA Based Epitope Vaccines for Alzheimers Disease Immunotherapy
CNS & Neurological Disorders - Drug Targets Conventional and Non-Conventional Targets of Natural Products in the Management of Diabetes Mellitus and Associated Complications
Current Medicinal Chemistry Role of Dietary Polyphenols in Attenuating Brain Edema and Cell Swelling in Cerebral Ischemia
Recent Patents on CNS Drug Discovery (Discontinued) Oxidative Stress: Apoptosis in Neuronal Injury
Current Alzheimer Research Therapeutic Agents in Alzheimer's Disease Through a Multi-targetdirected Ligands Strategy: Recent Progress Based on Tacrine Core
Current Topics in Medicinal Chemistry YKL-40 as a Potential Biomarker and a Possible Target in Therapeutic Strategies of Alzheimer’s Disease
Current Neuropharmacology Coenzyme Q10 for Patients with Parkinson's Disease: A Systematic Review and Meta-Analysis
CNS & Neurological Disorders - Drug Targets White Matter Integrity in Subcortical Vascular Cognitive Impairment: A Multimodal Structural MRI Study
Current Alzheimer Research Association Between the Levels of Circulating Adhesion Molecules and Biopterins in Type-2 Diabetic Normotensive Patients Adhesion Molecules and Biopterins
Endocrine, Metabolic & Immune Disorders - Drug Targets UCP2 and CFH Gene Variants with Genetic Susceptibility to Schizophrenia in Turkish Population
Endocrine, Metabolic & Immune Disorders - Drug Targets Minocycline and Cytoprotection: Shedding New Light on a Shadowy Controversy
Current Drug Delivery Metric Distances between Hippocampal Shapes Indicate Different Rates of Change over Time in Nondemented and Demented Subjects
Current Alzheimer Research Alzhemed: A Potential Treatment for Alzheimers Disease
Current Alzheimer Research Editorial [Hot topic: Alzheimers Disease Drug Discovery: Aβ and Beyond (Guest Editors: D.W. Shineman and H.M. Fillit)]
Current Alzheimer Research Cortical and Putamen Age-Related Changes in the Microvessel Density and Astrocyte Deficiency in Spontaneously Hypertensive and Stroke-Prone Spontaneously Hypertensive Rats
Current Neurovascular Research Pharmacological Management of Huntingtons Disease: An Evidence- Based Review
Current Pharmaceutical Design Nanoparticle Delivery of Transition-Metal Chelators to the Brain: Oxidative Stress will Never See it Coming!
CNS & Neurological Disorders - Drug Targets Ferric Cycle Activity and Alzheimer Disease
Current Neurovascular Research Heat Shock Proteins as Suppressors of Accumulation of Toxic Prefibrillar Intermediates and Misfolded Proteins in Neurodegenerative Diseases
Current Pharmaceutical Biotechnology Editorial [Hot topic: Polyunsaturated Fatty Acids and Human Health: A Critical Appraisal of the Evidence (Executive Editor: Antonio Cherubini)]
Current Pharmaceutical Design