Abstract
Individuals with trisomy 21, also known as Down syndrome (DS), develop a clinical syndrome including almost identical neuropathological characteristics of Alzheimers disease (AD) observed in non-DS individuals. The main difference is the early age of onset of AD pathology in individuals with DS, with high incidence of clinical symptoms in the late 40- early 50 years of age. The neuropathology of AD in persons with DS is superimposed with the developmental abnormalities causing alterations of neuronal morphology and function. Despite the ubiquitous occurrence of AD neuropathology, clinical signs of dementia do not occur in all adults with DS even at older ages. Phenotype analysis of DS mouse models has revealed a differential age-related neurodegenerative pattern that correlates with specific biochemical and molecular alterations at the cellular level. In fact, several individual genes found in trisomy in DS have been functionally related to neuronal degeneration. Thus, mouse models overexpressing HSA21 gene(s) are fundamental to understand the neurodegenerative process in DS, as described in the present review. In addition, these models might allow to define and evaluate potential drug targets and to develop therapeutic strategies that may interfere or delay the onset of AD.
Keywords: Down syndrome, Alzheimer's disease, neurodegeneration, HSA21 genes, mouse models
CNS & Neurological Disorders - Drug Targets
Title: Insights from Mouse Models to Understand Neurodegeneration in Down Syndrome
Volume: 9 Issue: 4
Author(s): Cristina Fillat, Mara Dierssen, Maria Martinez de Lagran and Xavier Altafaj
Affiliation:
Keywords: Down syndrome, Alzheimer's disease, neurodegeneration, HSA21 genes, mouse models
Abstract: Individuals with trisomy 21, also known as Down syndrome (DS), develop a clinical syndrome including almost identical neuropathological characteristics of Alzheimers disease (AD) observed in non-DS individuals. The main difference is the early age of onset of AD pathology in individuals with DS, with high incidence of clinical symptoms in the late 40- early 50 years of age. The neuropathology of AD in persons with DS is superimposed with the developmental abnormalities causing alterations of neuronal morphology and function. Despite the ubiquitous occurrence of AD neuropathology, clinical signs of dementia do not occur in all adults with DS even at older ages. Phenotype analysis of DS mouse models has revealed a differential age-related neurodegenerative pattern that correlates with specific biochemical and molecular alterations at the cellular level. In fact, several individual genes found in trisomy in DS have been functionally related to neuronal degeneration. Thus, mouse models overexpressing HSA21 gene(s) are fundamental to understand the neurodegenerative process in DS, as described in the present review. In addition, these models might allow to define and evaluate potential drug targets and to develop therapeutic strategies that may interfere or delay the onset of AD.
Export Options
About this article
Cite this article as:
Fillat Cristina, Dierssen Mara, Martinez de Lagran Maria and Altafaj Xavier, Insights from Mouse Models to Understand Neurodegeneration in Down Syndrome, CNS & Neurological Disorders - Drug Targets 2010; 9 (4) . https://dx.doi.org/10.2174/187152710791556159
DOI https://dx.doi.org/10.2174/187152710791556159 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
- 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
-
Exploiting the Diversity of the Heat-Shock Protein Family for Primary and Secondary Tauopathy Therapeutics
Current Neuropharmacology Vascular, Oxidative, and Synaptosomal Abnormalities During Aging and the Progression of Type 2 Diabetes
Current Neurovascular Research Recombinant Antibody Fragments for Neurodegenerative Diseases
Current Neuropharmacology Applications of Chemical Shift Imaging for AD
Current Medical Imaging Synthesis, Molecular Docking and Antiamnesic Activity of Selected 2- Naphthyloxy Derivatives
Medicinal Chemistry Cyclic AMP Enhancers and Aβ Oligomerization Blockers as Potential Therapeutic Agents in Alzheimers Disease
Current Alzheimer Research Established and In-trial GPCR Families in Clinical Trials: A Review for Target Selection
Current Drug Targets Amygdalar Atrophy in Early Alzheimer’s Disease
Current Alzheimer Research Substance P and Alzheimer’s Disease: Emerging Novel Roles
Current Alzheimer Research Targets of Antidementive Therapy: Drugs with a Specific Pharmacological Mechanism of Action
Current Pharmaceutical Design PDE4D Gene in the STRK1 Region on 5q12: Susceptibility Gene for Ischemic Stroke
Current Medicinal Chemistry Lipoprotein (a) Evolution: Possible Benefits and Harm. Genetic and Non-Genetic Factors Influencing its Plasma Levels
Current Medicinal Chemistry Structure Diversity, Synthesis, and Biological Activity of Cyathane Diterpenoids in Higher Fungi
Current Medicinal Chemistry Point of NO Return for Nitrergic Nerves in Diabetes: A New Insight into Diabetic Complications
Current Pharmaceutical Design Alterations of the X Chromosome in Lymphocytes of Alzheimer’s Disease Patients
Current Alzheimer Research Functional Genomics Approach for Identification of Molecular Processes Underlying Neurodegenerative Disorders in Prion Diseases
Current Genomics Mitochondria as a Therapeutic Target for Aging and Neurodegenerative Diseases
Current Alzheimer Research Vascular Contribution to Alzheimer Disease: Predictors of Rapid Progression
CNS & Neurological Disorders - Drug Targets Mitochondrial Disorders in Adults
Current Molecular Medicine Donepezil Base: Physicochemical Characterization, HPLC Method Development, Validation and its Application for the Determination of Shelf Life in Developed Solid Lipid Nanoparticles
Current Nanomedicine