Abstract
Down syndrome (DS) is the most common genetically defined cause of intellectual disability and accounts for over 50% of the cases of Alzheimer-type dementia in persons younger than 50 years of age. At present, no pharmacotherapy aimed at counteracting either the neurodevelopmental or the neurodegenerative component of this genetic disorder has been approved. Recent preclinical and clinical work on the N-methyl-D-aspartate (NMDA) receptor antagonist memantine give us some reason for optimism, at least in relation to the potential for a partial pharmacological improvement of hippocampus dependent memory deficits associated with DS. Here, we will review briefly the roles of NMDA receptors in health and disease, including the glutamatergic hypothesis for Alzheimer disease. Then, we will describe the basis for a glutamatergic hypothesis for DS, by reviewing the available preclinical evidence and assessing potential molecular mechanisms for NMDA receptor dysfunction in DS. A short description of the first two clinical trials of memantine in young and older adults with DS will follow. We will conclude by reviewing three caregiver reports from our recent clinical study and some lessons we have learned designing and conducting the first translational study in the field of DS to arise directly from experimental results in animal models.
Keywords: Down syndrome, Alzheimer disease, Trisomy 21, Ts65Dn mouse, Memantine, N-methyl-D-aspartate receptor, Long-term potentiation, Long-term depression.
CNS & Neurological Disorders - Drug Targets
Title:The Glutamatergic Hypothesis for Down Syndrome: The Potential Use of N-Methyl-D-Aspartate Receptor Antagonists to Enhance Cognition and Decelerate Neurodegeneration
Volume: 13 Issue: 1
Author(s): Alberto C.S. Costa
Affiliation:
Keywords: Down syndrome, Alzheimer disease, Trisomy 21, Ts65Dn mouse, Memantine, N-methyl-D-aspartate receptor, Long-term potentiation, Long-term depression.
Abstract: Down syndrome (DS) is the most common genetically defined cause of intellectual disability and accounts for over 50% of the cases of Alzheimer-type dementia in persons younger than 50 years of age. At present, no pharmacotherapy aimed at counteracting either the neurodevelopmental or the neurodegenerative component of this genetic disorder has been approved. Recent preclinical and clinical work on the N-methyl-D-aspartate (NMDA) receptor antagonist memantine give us some reason for optimism, at least in relation to the potential for a partial pharmacological improvement of hippocampus dependent memory deficits associated with DS. Here, we will review briefly the roles of NMDA receptors in health and disease, including the glutamatergic hypothesis for Alzheimer disease. Then, we will describe the basis for a glutamatergic hypothesis for DS, by reviewing the available preclinical evidence and assessing potential molecular mechanisms for NMDA receptor dysfunction in DS. A short description of the first two clinical trials of memantine in young and older adults with DS will follow. We will conclude by reviewing three caregiver reports from our recent clinical study and some lessons we have learned designing and conducting the first translational study in the field of DS to arise directly from experimental results in animal models.
Export Options
About this article
Cite this article as:
Costa C.S. Alberto, The Glutamatergic Hypothesis for Down Syndrome: The Potential Use of N-Methyl-D-Aspartate Receptor Antagonists to Enhance Cognition and Decelerate Neurodegeneration, CNS & Neurological Disorders - Drug Targets 2014; 13 (1) . https://dx.doi.org/10.2174/18715273113126660183
DOI https://dx.doi.org/10.2174/18715273113126660183 |
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
-
Spinal Microvascular Expression of PV-1 is Associated with Inflammation, Perivascular Astrocyte Loss, and Diminished EC Glucose Transport Potential in Acute SCI
Current Neurovascular Research The Nuclear Molecular Imaging of Protein Brain Receptors in Chronic Pain
Current Protein & Peptide Science Low Dose of Anisodine Hydrobromide Induced Neuroprotective Effects in Chronic Cerebral Hypoperfusion Rats
CNS & Neurological Disorders - Drug Targets Development of Polymeric Nanocarriers for Brain Targeted Delivery of Atorvastatin: A Quality-By-Design Approach
Drug Delivery Letters Genetic Markers in Biological Fluids for Aging-Related Major Neurocognitive Disorder
Current Alzheimer Research Mitophagy in Neurodegeneration: An Opportunity for Therapy?
Current Drug Targets The Prevalence of Frailty in Patients Admitted to Hospital with Vertebral Fragility Fractures
Current Rheumatology Reviews Genetic Variability of Matrix Metalloproteinase Genes in Cardiovascular Disease
Current Topics in Medicinal Chemistry Neurotrophic Factors as a Protective Strategy in Parkinsons Disease
CNS & Neurological Disorders - Drug Targets Nanotechnological Advances in the Treatment of Epilepsy
CNS & Neurological Disorders - Drug Targets G-Lymphatic, Vascular and Immune Pathways for Aβ Clearance Cascade and Therapeutic Targets For Alzheimer’s Disease
Combinatorial Chemistry & High Throughput Screening Total Bakkenolides Protects Neurons Against Cerebral Ischemic Injury Through Inhibition of Nuclear Factor-κB Activation
CNS & Neurological Disorders - Drug Targets Conference Report [IANR V and 9th GCNN Conference with 4th ISCITT Symposium]
CNS & Neurological Disorders - Drug Targets Modulation of GABAA Receptors by Natural Products and the Development of Novel Synthetic Ligands for the Benzodiazepine Binding Site
Current Drug Targets Fibrates and Microvascular Complications in Diabetes - Insight from the FIELD Study
Current Pharmaceutical Design Pathogens and Chronic or Long-Term Neurologic Disorders
Cardiovascular & Hematological Disorders-Drug Targets Hybrid SPECT/CT Imaging in Neurology
Current Radiopharmaceuticals Pre-CKD- Do we Need Another Hero?
Current Vascular Pharmacology Topical and Transdermal Delivery of Drug-Loaded Nano/ Microsystems with Application of Physical Enhancement Techniques
Current Drug Targets Neurosteroids and Sporadic Alzheimers Disease
Current Alzheimer Research