Abstract
MicroRNAs are small RNAs involved in gene silencing. They play important roles in transcriptional regulation and are selectively and abundantly expressed in the central nervous system. A considerable amount of the human genome is comprised of tandem repeating nucleotide streams. Several diseases are caused by above-threshold expansion of certain trinucleotide repeats occurring in a protein-coding or non-coding region. Though monogenic, CAG trinucleotide repeat expansion disorders have a complex pathogenesis, various combinations of multiple coexisting pathways resulting in one common final consequence: selective neurodegeneration. Mutant protein and mutant transcript gain of toxic function are considered to be the core pathogenic mechanisms. The profile of microRNAs in CAG trinucleotide repeat disorders is scarcely described, however microRNA dysregulation has been identified in these diseases and microRNA-related intereference with gene expression is considered to be involved in their pathogenesis. Better understanding of microRNAs functions and means of manipulation promises to offer further insights into the pathogenic pathways of CAG repeat expansion disorders, to point out new potential targets for drug intervention and to provide some of the much needed etiopathogenic therapeutic agents. A number of disease-modifying microRNA silencing strategies are under development, but several implementation impediments still have to be resolved. CAG targeting seems feasible and efficient in animal models and is an appealing approach for clinical practice. Preliminary human trials are just beginning.
Keywords: CAG, Huntington, microRNA, RNA interference, spinocerebellar, trinucleotide.
CNS & Neurological Disorders - Drug Targets
Title:MicroRNAs in CAG Trinucleotide Repeat Expansion Disorders: an Integrated Review of the Literature
Volume: 14 Issue: 2
Author(s): Laura Dumitrescu and Bogdan O. Popescu
Affiliation:
Keywords: CAG, Huntington, microRNA, RNA interference, spinocerebellar, trinucleotide.
Abstract: MicroRNAs are small RNAs involved in gene silencing. They play important roles in transcriptional regulation and are selectively and abundantly expressed in the central nervous system. A considerable amount of the human genome is comprised of tandem repeating nucleotide streams. Several diseases are caused by above-threshold expansion of certain trinucleotide repeats occurring in a protein-coding or non-coding region. Though monogenic, CAG trinucleotide repeat expansion disorders have a complex pathogenesis, various combinations of multiple coexisting pathways resulting in one common final consequence: selective neurodegeneration. Mutant protein and mutant transcript gain of toxic function are considered to be the core pathogenic mechanisms. The profile of microRNAs in CAG trinucleotide repeat disorders is scarcely described, however microRNA dysregulation has been identified in these diseases and microRNA-related intereference with gene expression is considered to be involved in their pathogenesis. Better understanding of microRNAs functions and means of manipulation promises to offer further insights into the pathogenic pathways of CAG repeat expansion disorders, to point out new potential targets for drug intervention and to provide some of the much needed etiopathogenic therapeutic agents. A number of disease-modifying microRNA silencing strategies are under development, but several implementation impediments still have to be resolved. CAG targeting seems feasible and efficient in animal models and is an appealing approach for clinical practice. Preliminary human trials are just beginning.
Export Options
About this article
Cite this article as:
Dumitrescu Laura and Popescu O. Bogdan, MicroRNAs in CAG Trinucleotide Repeat Expansion Disorders: an Integrated Review of the Literature, CNS & Neurological Disorders - Drug Targets 2015; 14 (2) . https://dx.doi.org/10.2174/1871527314666150116124715
DOI https://dx.doi.org/10.2174/1871527314666150116124715 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
Call for Papers in Thematic Issues
Diagnosis and treatment of central nervous system infectious diseases
Infectious diseases of the central nervous system (CNS) can be divided into bacterial, tuberculous, viral, fungal, parasitic infections, etc. Early etiological treatment is often the most crucial means to reduce the mortality rate of patients with central nervous system infections, reduce complications and sequelae, and improve prognosis. The initial clinical ...read more
Techniques of Drug Repurposing: Delivering a new life to Herbs & Drugs
Of late, with the adaptation of innovative approaches and integration of advancements made towards medical sciences as well as the availability of a wide range of tools; several therapeutic challenges are being translated into viable clinical solutions, with a high degree of efficacy, safety, and selectivity. With a better understanding ...read more
Trends and perspectives in the rational management of CNS disorders
Central nervous system (CNS) diseases enforce a significant global health burden, driving ongoing efforts to improve our understanding and effectiveness of therapy. This issue investigates current advances in the discipline, focusing on the understanding as well as therapeutic handling of various CNS diseases. The issue covers a variety of diseases, ...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
Related Articles
-
Epilepsy, Comorbidities and Treatments
Current Pharmaceutical Design Epilepsy, Regulation of Brain Energy Metabolism and Neurotransmission
Current Medicinal Chemistry Established and In-trial GPCR Families in Clinical Trials: A Review for Target Selection
Current Drug Targets Synthesis and Anticonvulsant Activity of Some Cinnamylpiperazine Derivatives
Letters in Drug Design & Discovery In Silico Validation and Structure Activity Relationship Study of a Series of Pyridine-3-carbohydrazide Derivatives as Potential Anticonvulsants in Generalized and Partial Seizures
Central Nervous System Agents in Medicinal Chemistry Neuroinflamm-Aging and Neurodegenerative Diseases: An Overview
CNS & Neurological Disorders - Drug Targets Structural Chromosome Abnormalities Associated with Obesity: Report of Four New Subjects and Review of Literature
Current Genomics New Insights in Prolactin Releasing Peptide (Prrp) in the Brain
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Adiponectin and its Role in Cardiovascular Diseases
Cardiovascular & Hematological Disorders-Drug Targets Preface
Current Drug Targets - CNS & Neurological Disorders Preventive and Therapeutic Effects of the Retinoid X Receptor Agonist Bexarotene on Tumors
Current Drug Metabolism Molecular Biomarkers for Amyotrophic Lateral Sclerosis
Current Bioinformatics Is VEGF a Key Target of Cotinine and Other Potential Therapies Against Alzheimer Disease?
Current Alzheimer Research A Review of Agents Patented for their Neuroprotective Properties
Recent Patents on CNS Drug Discovery (Discontinued) The Brain Protective Effect of rTMS (Repetitive Transcranial Magnetic Stimulation) in Depression: A Mini-Review in Animal Studies
Medicinal Chemistry Adult Hippocampal Neurogenesis as Target for the Treatment of Depression
CNS & Neurological Disorders - Drug Targets Glial Modulation of GABAergic and Glutamat ergic Neurotransmission
Current Topics in Medicinal Chemistry Clinical Features of Scleroderma-Like Disorders: A Challenge for the Rheumatologist
Current Rheumatology Reviews Metabolic Reprogramming of Human Cells in Response to Oxidative Stress: Implications in the Pathophysiology and Therapy of Mitochondrial Diseases
Current Pharmaceutical Design Involvement of microRNA-146a in the Inflammatory Response of S tatus Epilepticus Rats
CNS & Neurological Disorders - Drug Targets