Abstract
The polyglutamine (polyQ) diseases including Huntington’s disease and spinocerebellar ataxias are a group of inherited neurodegenerative diseases that are caused by an abnormal expansion of the polyQ stretch in disease-causative proteins. The expanded polyQ stretches are intrinsically unstable and are prone to form insoluble aggregates and inclusion bodies. Recent studies have revealed that the expanded polyQ proteins gain cytotoxicity during the aggregation process, which may possibly cause detrimental effects on a wide range of essential cellular functions leading to eventual neuronal degeneration. Based on the pathogenic mechanism of the polyQ diseases, several therapeutic approaches have been proposed to date. Among them, here we focus on peptide-based approaches that target either aggregate formation of the polyQ proteins or abnormal cellular processes induced by the expanded polyQ proteins. Although both approaches are effective in suppressing cytotoxicity of the abnormal polyQ proteins and the disease phenotypes of animal models, the former approach is more attractive since it targets the most upstream change occurring in the polyQ diseases, and is therefore expected to be effective against various downstream functional abnormalities in a broad range of polyQ diseases. One of the major current problems that must be overcome for development of peptide-based therapies of the polyQ diseases is the issue of brain delivery, which is also discussed in this article. We hope that in the near future effective therapies are developed, and bring hope to many patients suffering from the currently untreatable polyQ diseases.
Keywords: Neurodegeneration, peptide, polyglutamine diseases, protein aggregation, therapy.
Current Medicinal Chemistry
Title:Peptide-Based Therapeutic Approaches for Treatment of the Polyglutamine Diseases
Volume: 21 Issue: 23
Author(s): Toshihide Takeuchi, H. Akiko Popiel, Shiroh Futaki, Keiji Wada and Yoshitaka Nagai
Affiliation:
Keywords: Neurodegeneration, peptide, polyglutamine diseases, protein aggregation, therapy.
Abstract: The polyglutamine (polyQ) diseases including Huntington’s disease and spinocerebellar ataxias are a group of inherited neurodegenerative diseases that are caused by an abnormal expansion of the polyQ stretch in disease-causative proteins. The expanded polyQ stretches are intrinsically unstable and are prone to form insoluble aggregates and inclusion bodies. Recent studies have revealed that the expanded polyQ proteins gain cytotoxicity during the aggregation process, which may possibly cause detrimental effects on a wide range of essential cellular functions leading to eventual neuronal degeneration. Based on the pathogenic mechanism of the polyQ diseases, several therapeutic approaches have been proposed to date. Among them, here we focus on peptide-based approaches that target either aggregate formation of the polyQ proteins or abnormal cellular processes induced by the expanded polyQ proteins. Although both approaches are effective in suppressing cytotoxicity of the abnormal polyQ proteins and the disease phenotypes of animal models, the former approach is more attractive since it targets the most upstream change occurring in the polyQ diseases, and is therefore expected to be effective against various downstream functional abnormalities in a broad range of polyQ diseases. One of the major current problems that must be overcome for development of peptide-based therapies of the polyQ diseases is the issue of brain delivery, which is also discussed in this article. We hope that in the near future effective therapies are developed, and bring hope to many patients suffering from the currently untreatable polyQ diseases.
Export Options
About this article
Cite this article as:
Takeuchi Toshihide, Popiel Akiko H., Futaki Shiroh, Wada Keiji and Nagai Yoshitaka, Peptide-Based Therapeutic Approaches for Treatment of the Polyglutamine Diseases, Current Medicinal Chemistry 2014; 21 (23) . https://dx.doi.org/10.2174/0929867321666140217124038
DOI https://dx.doi.org/10.2174/0929867321666140217124038 |
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 Underlying Role of Oxidative Stress in Neurodegeneration: A Mechanistic Review
CNS & Neurological Disorders - Drug Targets Role of the α7 Nicotinic Acetylcholine Receptor and RIC-3 in the Cholinergic Anti-inflammatory Pathway
Central Nervous System Agents in Medicinal Chemistry Improvement of Microscopic MR Imaging of Amyloid Plaques with Targeting and Non-Targeting Contrast Agents
Current Medical Imaging Metabotropic Glutamate Receptors (mGluRs) and Diabetic Neuropathy
Current Drug Targets New Therapeutic Property of Dimebon as a Neuroprotective Agent
Current Medicinal Chemistry Adenosine and Related Drugs in Brain Diseases: Present and Future in Clinical Trials
Current Topics in Medicinal Chemistry Possible Impact of Microglial Cells and the Monocyte-Macrophage System on Suicidal Behavior
CNS & Neurological Disorders - Drug Targets Advanced Glycation End Products, Oxidative Stress and Metalloproteinases are altered in the Cerebral Microvasculature during Aging
Current Neurovascular Research Editorial [Continue the Great Journey of Success!]
Current Molecular Medicine Probing Multidrug Resistance P-glycoprotein Transporter Activity with SPECT Radiopharmaceuticals
Current Topics in Medicinal Chemistry Imaging β-Amyloid Plaques and Neurofibrillary Tangles in the Aging Human Brain
Current Pharmaceutical Design Characterization of Pharmaceutical IgG and Biosimilars Using Miniaturized Platforms and LC-MS/MS
Current Pharmaceutical Biotechnology A Review on Structures and Functions of Bcl-2 Family Proteins from Homo sapiens
Protein & Peptide Letters The Role of Lipids and Membranes in the Pathogenesis of Alzheimer's Disease: A Comprehensive View
Current Alzheimer Research Differential Kat3 Coactivator Usage Regulates Brain Metabolism and Neuronal Differentiation
Current Molecular Pharmacology Challenges in the Discovery of Novel Therapeutic Agents for Cancer Treatment (Part IV)
Current Drug Metabolism Heat Shock Protein (HSP) Drug Discovery and Development: Targeting Heat Shock Proteins in Disease
Current Topics in Medicinal Chemistry Role of Flavonoids in Neurodegenerative Disorders with Special Emphasis on Tangeritin
CNS & Neurological Disorders - Drug Targets Prediction and Targeting of Interaction Interfaces in G-protein Coupled Receptor Oligomers
Current Topics in Medicinal Chemistry Recent Progress Toward Hydrogen Medicine: Potential of Molecular Hydrogen for Preventive and Therapeutic Applications
Current Pharmaceutical Design