Abstract
Down syndrome (DS), the most common genetic cause of intellectual disability, is caused by the trisomy of chromosome 21. MNB/DYRK1A (Minibrain/dual specificity tyrosine phosphorylation-regulated kinase 1A) has possibly been the most extensively studied chromosome 21 gene during the last decade due to the remarkable correlation of its functions in the brain with important DS neuropathologies, such as neuronal deficits, dendrite atrophy, spine dysgenesis, precocious Alzheimer’s-like neurodegeneration, and cognitive deficits. MNB/DYRK1A has become an attractive drug target because increasing evidence suggests that its overexpression may induce DS-like neurobiological alterations, and several small-molecule inhibitors of its protein kinase activity are available. Here, we summarize the functional complexity of MNB/DYRK1A from a DS-research perspective, paying particular attention to the capacity of different MNB/DYRK1A inhibitors to reverse the neurobiological alterations caused by the increased activity of MNB/DYRK1A in experimental models. Finally, we discuss the advantages and drawbacks of possible MNB/DYRK1A-based therapeutic strategies that result from the functional, molecular, and pharmacological complexity of MNB/DYRK1A.
Keywords: Down syndrome, minibrain, neuropathologies, cognitive deficit, trisomy 21, harmine, epigallocatechin-gallate.
CNS & Neurological Disorders - Drug Targets
Title:DYRK1A: A Potential Drug Target for Multiple Down Syndrome Neuropathologies
Volume: 13 Issue: 1
Author(s): Walter Becker, Ulf Soppa and Francisco J. Tejedor
Affiliation:
Keywords: Down syndrome, minibrain, neuropathologies, cognitive deficit, trisomy 21, harmine, epigallocatechin-gallate.
Abstract: Down syndrome (DS), the most common genetic cause of intellectual disability, is caused by the trisomy of chromosome 21. MNB/DYRK1A (Minibrain/dual specificity tyrosine phosphorylation-regulated kinase 1A) has possibly been the most extensively studied chromosome 21 gene during the last decade due to the remarkable correlation of its functions in the brain with important DS neuropathologies, such as neuronal deficits, dendrite atrophy, spine dysgenesis, precocious Alzheimer’s-like neurodegeneration, and cognitive deficits. MNB/DYRK1A has become an attractive drug target because increasing evidence suggests that its overexpression may induce DS-like neurobiological alterations, and several small-molecule inhibitors of its protein kinase activity are available. Here, we summarize the functional complexity of MNB/DYRK1A from a DS-research perspective, paying particular attention to the capacity of different MNB/DYRK1A inhibitors to reverse the neurobiological alterations caused by the increased activity of MNB/DYRK1A in experimental models. Finally, we discuss the advantages and drawbacks of possible MNB/DYRK1A-based therapeutic strategies that result from the functional, molecular, and pharmacological complexity of MNB/DYRK1A.
Export Options
About this article
Cite this article as:
Becker Walter, Soppa Ulf and Tejedor J. Francisco, DYRK1A: A Potential Drug Target for Multiple Down Syndrome Neuropathologies, CNS & Neurological Disorders - Drug Targets 2014; 13 (1) . https://dx.doi.org/10.2174/18715273113126660186
DOI https://dx.doi.org/10.2174/18715273113126660186 |
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
-
Atherosclerotic and Non-Atherosclerotic Coronary Heart Disease in Women
Current Medicinal Chemistry Targeting Inhibition of COX-2: A Review of Patents, 2002 - 2006
Recent Patents on Inflammation & Allergy Drug Discovery The Fetal Cardiac Function
Current Cardiology Reviews Statins in Stroke Prevention: Present and Future
Current Pharmaceutical Design Quantification and Pharmacokinetics Study of Pedunculoside in Rats by Using UPLC-MS/MS
Current Pharmaceutical Analysis Genetic Variations in Telomere Maintenance, with Implications on Tissue Renewal Capacity and Chronic Disease Pathologies
Current Pharmacogenomics and Personalized Medicine SDH Genes: From Glomic Tumours to Pheochromocytomas
Current Hypertension Reviews Understanding Heterogeneity in Supplementation Effects of Selenium in Men: A Study of Stratification Variables and Human Genetics in a Prospective Sample from New Zealand
Current Pharmacogenomics and Personalized Medicine Critical Review of the Ankle Brachial Index
Current Cardiology Reviews Modification of Lifestyle Factors are Needed to Improve the Metabolic Health of Patients with Cardiovascular Disease Risk
Current Pharmaceutical Design Potential Role of Inflammation in Associations between Particulate Matter and Heart Failure
Current Pharmaceutical Design Cardiovascular Magnetic Resonance Imaging clarifies cardiac pathophysiology in early, asymptomatic diffuse systemic sclerosis
Inflammation & Allergy - Drug Targets (Discontinued) Preface [Hot Topic: Recent Progress in Cardiovascular Gene Therapy;Emerging to Real Drug? (Guest Editor: Ryuichi Morishita)]
Current Gene Therapy Autologous Adipose-Derived Regenerative Cells for Therapeutic Angiogenesis
Current Pharmaceutical Design Development of Inhibitors of the Aspartyl Protease Renin for the Treatment of Hypertension
Current Protein & Peptide Science Imaging of Integrins as Biomarkers for Tumor Angiogenesis
Current Pharmaceutical Design The Cardiovascular Nutrapharmacology of Resveratrol: Pharmacokinetics, Molecular Mechanisms and Therapeutic Potential
Current Medicinal Chemistry Dynamics of Diabetes and Obesity: An Alarming Situation in the Developing Countries in Asia
Mini-Reviews in Medicinal Chemistry Mycobacterial DNA Replication as a Target for Antituberculosis Drug Discovery
Current Topics in Medicinal Chemistry Nutrigenetics, Metabolic Syndrome Risk and Personalized Nutrition
Current Vascular Pharmacology