Abstract
Alzheimer’s disease (AD) is the most common age-related neurodegenerative disorder among the elderly. Nmethyl- D-aspartate receptor (NMDAR) overactivation has been implicated in early synaptic dysfunction that precedes late neurodegeneration in AD. Moreover, oligomers of amyloid-beta peptide (Aβ) 1-42 are considered the most synaptotoxic forms, responsible for early cognitive deficits in AD. In this work we evaluate the role of NMDARs on Aβ-evoked neuronal dysfunction and cell death through changes in microtubule polymerization in mature hippocampal cultures. Exposure to Aβ 1-42 caused a decrease in total and polymerized levels of beta-III tubulin and polymerized alpha-tubulin, suggesting microtubule disassembly. Moreover, Aβ induced DNA fragmentation in both neuronal and non-neuronal cells. Indeed, the effects of Aβ on beta-III tubulin polymerization were significantly correlated with reduced neurite length and neuronal DNA fragmentation. Interestingly, these effects were prevented by MK-801 and memantine, suggesting a role for extrasynaptic NMDARs in Aβ toxicity, and by ifenprodil, further indicating the involvement of GluN2B-containing NMDARs. Nevertheless, exposure to Aβ did not potentiate the effects caused by selective activation of NMDARs. Data largely suggest that Aβ-induced hippocampal neuronal dysfunction occurs through NMDAR-dependent microtubule disassembly associated to neurite retraction and DNA fragmentation in mature hippocampal cells.
Keywords: Alzheimer’s disease, amyloid-beta peptide, DNA fragmentation, hippocampal cells, microtubules, NMDA receptors, GluN2B subunit, fluorescence microscopy.
Current Alzheimer Research
Title:Amyloid-Beta Peptide 1-42 Causes Microtubule Deregulation through N-methyl-D-aspartate Receptors in Mature Hippocampal Cultures
Volume: 9 Issue: 7
Author(s): Sandra I. Mota, Ildete L. Ferreira, Claudia Pereira, Catarina R. Oliveira and A. Cristina Rego
Affiliation:
Keywords: Alzheimer’s disease, amyloid-beta peptide, DNA fragmentation, hippocampal cells, microtubules, NMDA receptors, GluN2B subunit, fluorescence microscopy.
Abstract: Alzheimer’s disease (AD) is the most common age-related neurodegenerative disorder among the elderly. Nmethyl- D-aspartate receptor (NMDAR) overactivation has been implicated in early synaptic dysfunction that precedes late neurodegeneration in AD. Moreover, oligomers of amyloid-beta peptide (Aβ) 1-42 are considered the most synaptotoxic forms, responsible for early cognitive deficits in AD. In this work we evaluate the role of NMDARs on Aβ-evoked neuronal dysfunction and cell death through changes in microtubule polymerization in mature hippocampal cultures. Exposure to Aβ 1-42 caused a decrease in total and polymerized levels of beta-III tubulin and polymerized alpha-tubulin, suggesting microtubule disassembly. Moreover, Aβ induced DNA fragmentation in both neuronal and non-neuronal cells. Indeed, the effects of Aβ on beta-III tubulin polymerization were significantly correlated with reduced neurite length and neuronal DNA fragmentation. Interestingly, these effects were prevented by MK-801 and memantine, suggesting a role for extrasynaptic NMDARs in Aβ toxicity, and by ifenprodil, further indicating the involvement of GluN2B-containing NMDARs. Nevertheless, exposure to Aβ did not potentiate the effects caused by selective activation of NMDARs. Data largely suggest that Aβ-induced hippocampal neuronal dysfunction occurs through NMDAR-dependent microtubule disassembly associated to neurite retraction and DNA fragmentation in mature hippocampal cells.
Export Options
About this article
Cite this article as:
I. Mota Sandra, L. Ferreira Ildete, Pereira Claudia, R. Oliveira Catarina and Cristina Rego A., Amyloid-Beta Peptide 1-42 Causes Microtubule Deregulation through N-methyl-D-aspartate Receptors in Mature Hippocampal Cultures, Current Alzheimer Research 2012; 9 (7) . https://dx.doi.org/10.2174/156720512802455322
DOI https://dx.doi.org/10.2174/156720512802455322 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
Call for Papers in Thematic Issues
New Advances in the Prevention, Diagnosis, Treatment, and Rehabilitation of Alzheimer's Disease
Aims and Scope: Introduction: Alzheimer's disease (AD) poses a significant global health challenge, with an increasing prevalence that demands concerted efforts to advance our understanding and strategies for prevention, diagnosis, treatment, and rehabilitation. This thematic issue aims to bring together cutting-edge research and innovative approaches from multidisciplinary perspectives to address ...read more
Current updates on the Role of Neuroinflammation in Neurodegenerative Disorders
Neuroinflammation is an invariable hallmark of chronic and acute neurodegenerative disorders and has long been considered a potential drug target for Alzheimer?s disease (AD) and dementia. Significant evidence of inflammatory processes as a feature of AD is provided by the presence of inflammatory markers in plasma, CSF and postmortem brain ...read more
Deep Learning for Advancing Alzheimer's Disease Research
Alzheimer's disease (AD) poses a significant global health challenge, with an increasing number of individuals affected yearly. Deep learning, a subfield of artificial intelligence, has shown immense potential in various domains, including healthcare. This thematic issue of Current Alzheimer Research explores the application of deep learning techniques in advancing our ...read more
Diagnostic and therapeutic biomarkers of dementia
Dementia affects 18 million people worldwide. Dementia is a syndrome of symptoms caused by brain disease, usually chronic or progressive, clinically characterized by multiple impairments of higher cortical functions such as memory, thinking, orientation, and learning. In addition, in the course of dementia, cognitive deficits are observed, which often hinder ...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
-
GSK-3 Inhibitors in the Regulation and Control of Colon Carcinoma
Current Drug Targets Resistance to Peloruside A and Laulimalide: Functional Significance of Acquired βI-tubulin Mutations at Sites Important for Drug-Tubulin Binding
Current Cancer Drug Targets Patent Selections
Recent Patents on Drug Delivery & Formulation The Role of Ghrelin Signals in Breast Cancer- A Systematic Review
Current Signal Transduction Therapy Nonviral Vectors for Cancer Gene Therapy: Prospects for Integrating Vectors and Combination Therapies
Current Gene Therapy Novel Patents Targeting Interleukin-17A; Implications in Cancer and Inflammation
Recent Patents on Anti-Cancer Drug Discovery Current Targeting Strategies for Adenovirus Vectors in Cancer Gene Therapy
Current Cancer Drug Targets Gap Junctions as Therapeutic Targets in Brain Injury Following Hypoxia- Ischemia
Recent Patents on CNS Drug Discovery (Discontinued) Technologies for Translational Imaging Using Generators in Oncology
Recent Patents on Anti-Cancer Drug Discovery Curcumin Suppresses Tumor Growth and Angiogenesis in Human Glioma Cells Through Modulation of Vascular Endothelial Growth Factor/ Angiopoietin-2/Thrombospondin-1 Signaling
CNS & Neurological Disorders - Drug Targets Tumor-Receptor Imaging in Breast Cancer: A Tool for Patient Selection and Response Monitoring
Current Molecular Medicine Role of FoxM1 in the Progression and Epithelial to Mesenchymal Transition of Gastrointestinal Cancer
Recent Patents on Anti-Cancer Drug Discovery Emerging RNA-based Drugs: siRNAs, microRNAs and Derivates
Central Nervous System Agents in Medicinal Chemistry Xenobiotic Sulphation and its Variability During Inflammation: a Factor in Adverse Drug Reactions?
Current Drug Metabolism Targeting the p53-Family in Cancer and Chemosensitivity: Triple Threat
Current Drug Targets Peptides Targeting Gap Junctional Structures
Current Pharmaceutical Design Lysosomal Storage Diseases and the Blood-Brain Barrier
Current Pharmaceutical Design Apoptosis in Drug Response
Current Pharmacogenomics Targeting Receptor Tyrosine Kinases Using Monoclonal Antibodies: The Most Specific Tools for Targeted-Based Cancer Therapy
Current Drug Targets Immuno-Isolation in Cancer Gene Therapy
Current Gene Therapy