Abstract
Although cellular RNA should be subject to the same oxidative insults as DNA and other cellular macromolecules, oxidative damage to RNA has not been a major focus in investigating the magnitude and the biological consequences of the free radical damage. However, because RNA is mostly single-stranded and its bases are not protected by hydrogen bonding and are less protected by specific proteins, RNA may be more susceptible to oxidative insults than DNA. Thereafter, oxidative damage to protein-coding RNA or noncoding RNA will potentially cause errors in proteins or dysregulation of gene expression. While less lethal than mutations in genome, such non-acutely lethal insults to cells might be associated with underlying mechanisms of several human diseases, especially chronic degeneration. Recently, oxidative RNA damage has been described in several neurodegenerative diseases including Alzheimer disease, Parkinson disease, dementia with Lewy bodies, and prion diseases. Of particular interest, oxidative RNA damage is a feature in vulnerable neurons at the very earliest-stages of these diseases, suggesting that RNA oxidation may actively contribute to the onset or to the development of disease. Mechanistically speaking, an increasing body of evidence suggests that the detrimental effects of oxidative RNA damage to protein synthesis are attenuated, at least in part, by the existence of mechanisms that avoid the incorporation of the damaged ribonucleotides into the translational machinery. Further investigations toward understanding of the consequences and processing mechanisms related to oxidative RNA damage may provide significant insights into the pathogenesis and therapeutic strategies for neurodegenerative and other degenerative diseases.
Keywords: Alzheimer disease, 8-hydroxyguanosine, neurodegeneration, oxidative damage, Parkinson disease, RNA
Current Medicinal Chemistry
Title: Oxidative RNA Damage and Neurodegeneration
Volume: 14 Issue: 28
Author(s): A. Nunomura, P. I. Moreira, A. Takeda, M. A. Smith and G. Perry
Affiliation:
Keywords: Alzheimer disease, 8-hydroxyguanosine, neurodegeneration, oxidative damage, Parkinson disease, RNA
Abstract: Although cellular RNA should be subject to the same oxidative insults as DNA and other cellular macromolecules, oxidative damage to RNA has not been a major focus in investigating the magnitude and the biological consequences of the free radical damage. However, because RNA is mostly single-stranded and its bases are not protected by hydrogen bonding and are less protected by specific proteins, RNA may be more susceptible to oxidative insults than DNA. Thereafter, oxidative damage to protein-coding RNA or noncoding RNA will potentially cause errors in proteins or dysregulation of gene expression. While less lethal than mutations in genome, such non-acutely lethal insults to cells might be associated with underlying mechanisms of several human diseases, especially chronic degeneration. Recently, oxidative RNA damage has been described in several neurodegenerative diseases including Alzheimer disease, Parkinson disease, dementia with Lewy bodies, and prion diseases. Of particular interest, oxidative RNA damage is a feature in vulnerable neurons at the very earliest-stages of these diseases, suggesting that RNA oxidation may actively contribute to the onset or to the development of disease. Mechanistically speaking, an increasing body of evidence suggests that the detrimental effects of oxidative RNA damage to protein synthesis are attenuated, at least in part, by the existence of mechanisms that avoid the incorporation of the damaged ribonucleotides into the translational machinery. Further investigations toward understanding of the consequences and processing mechanisms related to oxidative RNA damage may provide significant insights into the pathogenesis and therapeutic strategies for neurodegenerative and other degenerative diseases.
Export Options
About this article
Cite this article as:
Nunomura A., Moreira I. P., Takeda A., Smith A. M. and Perry G., Oxidative RNA Damage and Neurodegeneration, Current Medicinal Chemistry 2007; 14 (28) . https://dx.doi.org/10.2174/092986707782794078
DOI https://dx.doi.org/10.2174/092986707782794078 |
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
-
The Role of Metabolizing Enzymes and Transporters in Antiretroviral Therapy
Current Topics in Medicinal Chemistry The Protective Role of Heme Oxygenase-1 in Cerebral Ischemia
Central Nervous System Agents in Medicinal Chemistry Multimodality Imaging in Acute Ischemic Stroke
Current Medical Imaging The Immunoproteasome: An Emerging Therapeutic Target
Current Topics in Medicinal Chemistry 99mTc-labeled Small Molecules for Diagnosis of Alzheimer’s Disease: Past, Recent and Future Perspectives
Current Medicinal Chemistry A Pilot Study of Exenatide Actions in Alzheimer’s Disease
Current Alzheimer Research Biochemical Markers and Risk Factors of Alzheimers Disease
Current Alzheimer Research Role of Sirtuins and Calorie Restriction in Neuroprotection: Implications in Alzheimers and Parkinsons Diseases
Current Pharmaceutical Design Sensory-Motor Integration in the Medial Medulla
Current Neuropharmacology Thromboembolic Complications in Malignant Haematological Disorders
Current Vascular Pharmacology Substance Abuse and Movement Disorders: Complex Interactions and Comorbidities
Current Drug Abuse Reviews Improvement in Hypertension Management with Pharmacological and Non- Pharmacological Approaches: Current Perspectives
Current Pharmaceutical Design Depression and Vascular Disease: Conceptual Issues, Relationships and Clinical Implications
Vascular Disease Prevention (Discontinued) Lipid Nanoparticles as Carriers for the Treatment of Neurodegeneration Associated with Alzheimer’s Disease and Glaucoma: Present and Future Challenges
Current Pharmaceutical Design Role of Hydrogen Sulfide and Polysulfides in Neurological Diseases: Focus on Protein S-Persulfidation
Current Neuropharmacology Etanercept Improves Cognitive Performance and Increases eNOS and BDNF Expression During Experimental Vascular Dementia in Streptozotocin- induced Diabetes
Current Neurovascular Research Genomics and the Prospects of Existing and Emerging Therapeutics for Cardiovascular Diseases
Current Pharmaceutical Design JNK Signalling: A Possible Target to Prevent Neurodegeneration
Current Pharmaceutical Design Kinetics of In Vitro Inhibition of Acetylcholinesterase by Nineteen New Carbamates
Current Enzyme Inhibition Neuroinflammation and Alzheimer's Disease: Implications for Microglial Activation
Current Alzheimer Research