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
![](/images/wayfinder.jpg)
- 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
-
Synthetic Strategies and Biological Potential of Coumarin-Chalcone Hybrids: A New Dimension to Drug Design
Current Organic Chemistry Polypharmacology in a Single Drug: Multitarget Drugs
Current Medicinal Chemistry Prolyl-Specific Peptidases and Their Inhibitors in Biological Processes
Current Chemical Biology Impact of Anabolic Androgenic Steroids on Neuropeptide Systems
Mini-Reviews in Medicinal Chemistry Cell Life Versus Cell Longevity: The Mysteries Surrounding the NAD+ Precursor Nicotinamide
Current Medicinal Chemistry The Prion-like Properties of Amyloid-beta Peptide and Tau: Is there Any Risk of Transmitting Alzheimer's Disease During Neurosurgical Interventions?
Current Alzheimer Research Editorial: Glia-Neuron Crosstalk and its Therapeutic Implication in Neuropsychiatric Disorders
Current Neuropharmacology Prognostic Significance of Homocysteine Levels in Acute Ischemic Stroke: A Prospective Cohort Study
Current Neurovascular Research A Comparison of Two Statistical Mapping Tools for Automated Brain FDG-PET Analysis in Predicting Conversion to Alzheimer’s Disease in Subjects with Mild Cognitive Impairment
Current Alzheimer Research Targeting JAK3 Tyrosine Kinase-Linked Signal Transduction Pathways with Rationally-Designed Inhibitors
Anti-Cancer Agents in Medicinal Chemistry Structural Preferences of Neuroprotective S14G-Humanin Peptide Analyzed by Molecular Modeling and Circular Dichroism
Protein & Peptide Letters Dynamic Role of Macrophage Sub Types on Development of Atherosclerosis and Potential Use of Herbal Immunomodulators as Imminent Therapeutic Strategy
Cardiovascular & Hematological Agents in Medicinal Chemistry Diagnosis of Alzheimer's Disease Based on Deeply-Fused Nets
Combinatorial Chemistry & High Throughput Screening Intranasal Delivery of Leuprolide Acetate Chitosan Nanoparticles for Treatment of Alzheimer’s Disease
Drug Delivery Letters Irbesartan and Hydrochlorothiazide Association in the Treatment of Hypertension
Current Vascular Pharmacology Need for Nutritious Convenience Foods for the Elderly Population: A Review
Current Nutrition & Food Science Ageing Mechanisms and Associated Lipid Changes
Current Vascular Pharmacology Cell Microencapsulation Implants into the Central Nervous System
Recent Patents on Nanomedicine Drainage of Cerebral Abscesses Prior to Valve Replacement in Stable Patients with Acute Left-Sided Infective Endocarditis
CNS & Neurological Disorders - Drug Targets Cognitive Dysfunction in Depression: Lessons Learned from Animal Models
CNS & Neurological Disorders - Drug Targets