Abstract
One mechanism leading to neurodegeneration during Alzheimers Disease (AD) is amyloid β peptide (Aβ)- induced neurotoxicity. Among the factors proposed to potentiate Aβ toxicity is its covalent modification through carbohydrate- derived advanced glycation endproducts (AGEs). Other experimental evidence, though, indicates that certain polymeric carbohydrates like the glycosaminoglycan (GAG) chains found in proteoglycan molecules attenuate the neurotoxic effect of Aβ in primary neuronal cultures. Pretreatment of the 42-residue Aβ fragment (Aβ1-42) with the ubiquitous brain carbohydrates, glucose, fructose, and the GAG chondroitin sulfate B (CSB) inhibits Aβ1-42-induced apoptosis and reduces the peptide neurotoxicity on neuroblastoma cells, a cytoprotective effect that is partially reverted by AGE inhibitors such as pyridoxamine and L-carnosine. Thioflavin T fluorescence measurements indicate that at concentrations close to physiological, only CSB promotes the formation of Aβ amyloid fibril structure. Atomic force microscopy imaging and Western blot analysis suggest that glucose favours the formation of globular oligomeric structures derived from aggregated species. Our data suggest that at short times carbohydrates reduce Aβ1-42 toxicity through different mechanisms both dependent and independent of AGE formation.
Keywords: Alzheimer's disease, advanced glycation endproducts, amyloid fibrils, amyloid β peptide, apoptosis, carbohydrates, glycosaminoglycans
Current Alzheimer Research
Title: Modulation of Amyloid β Peptide1-42 Cytotoxicity and Aggregation in Vitro by Glucose and Chondroitin Sulfate
Volume: 7 Issue: 5
Author(s): X. Fernandez-Busquets, J. Ponce, R. Bravo, M. Arimon, T. Martianez, A. Gella, J. Cladera and N. Durany
Affiliation:
Keywords: Alzheimer's disease, advanced glycation endproducts, amyloid fibrils, amyloid β peptide, apoptosis, carbohydrates, glycosaminoglycans
Abstract: One mechanism leading to neurodegeneration during Alzheimers Disease (AD) is amyloid β peptide (Aβ)- induced neurotoxicity. Among the factors proposed to potentiate Aβ toxicity is its covalent modification through carbohydrate- derived advanced glycation endproducts (AGEs). Other experimental evidence, though, indicates that certain polymeric carbohydrates like the glycosaminoglycan (GAG) chains found in proteoglycan molecules attenuate the neurotoxic effect of Aβ in primary neuronal cultures. Pretreatment of the 42-residue Aβ fragment (Aβ1-42) with the ubiquitous brain carbohydrates, glucose, fructose, and the GAG chondroitin sulfate B (CSB) inhibits Aβ1-42-induced apoptosis and reduces the peptide neurotoxicity on neuroblastoma cells, a cytoprotective effect that is partially reverted by AGE inhibitors such as pyridoxamine and L-carnosine. Thioflavin T fluorescence measurements indicate that at concentrations close to physiological, only CSB promotes the formation of Aβ amyloid fibril structure. Atomic force microscopy imaging and Western blot analysis suggest that glucose favours the formation of globular oligomeric structures derived from aggregated species. Our data suggest that at short times carbohydrates reduce Aβ1-42 toxicity through different mechanisms both dependent and independent of AGE formation.
Export Options
About this article
Cite this article as:
Fernandez-Busquets X., Ponce J., Bravo R., Arimon M., Martianez T., Gella A., Cladera J. and Durany N., Modulation of Amyloid β Peptide1-42 Cytotoxicity and Aggregation in Vitro by Glucose and Chondroitin Sulfate, Current Alzheimer Research 2010; 7 (5) . https://dx.doi.org/10.2174/156720510791383787
DOI https://dx.doi.org/10.2174/156720510791383787 |
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
-
The Concept of Dysregulated Signal Transduction and Gene Expression in the Pathophysiology of Mood Disorders
Current Psychiatry Reviews Phenolic and Organic Acids from <i>Spondias pinnata</i> Fruits
The Natural Products Journal Mechanism of Tau-Induced Neurodegeneration in Alzheimer Disease and Related Tauopathies
Current Alzheimer Research Signal Pathways Mediating Antidepressant and Antipsychotic Drugs on Neuronal Cell Survival
Current Medicinal Chemistry - Central Nervous System Agents HSP90 Inhibitors: Multi-Targeted Antitumor Effects and Novel Combinatorial Therapeutic Approaches in Cancer Therapy
Current Medicinal Chemistry Gut Emotions - Mechanisms of Action of Probiotics as Novel Therapeutic Targets for Depression and Anxiety Disorders
CNS & Neurological Disorders - Drug Targets The Exploitation of Toll-like Receptor 3 Signaling in Cancer Therapy
Current Pharmaceutical Design Therapeutic microRNA Delivery Strategies with Special Emphasis on Cancer Therapy and Tumorigenesis: Current Trends and Future Challenges
Current Drug Metabolism Roles of Nicotinic Acetylcholine Receptors in Stem Cell Survival/Apoptosis, Proliferation and Differentiation
Current Molecular Medicine Biochemical Characterization of Apoptotic Cleavage of KH-Type Splicing Regulatory Protein (KSRP) / Far Upstream Element-Binding Protein 2 (FBP2)
Protein & Peptide Letters Recombinant Antibody Fragments for Neurodegenerative Diseases
Current Neuropharmacology HDAC Inhibitors-New Generation of Target Specific Treatment
Mini-Reviews in Medicinal Chemistry Glycogen Synthase Kinase-3 (GSK-3) Inhibitors for the Treatment of Alzheimers Disease
Current Pharmaceutical Design Dendritoma Vaccine for Cancer: A Hopeful Approach
Current Cancer Therapy Reviews Metal Ions and Metal Complexes in Alzheimer’s Disease
Current Pharmaceutical Design Design, Synthesis and Evaluation of Novel 2-piperidinyl Quinoline Chalcones/ Amines as Potential Antidepressant Agents
Letters in Drug Design & Discovery New Classes of AChE Inhibitors with Additional Pharmacological Effects of Interest for the Treatment of Alzheimers Disease
Current Pharmaceutical Design Edelfosine in Membrane Environment - the Langmuir Monolayer Studies
Anti-Cancer Agents in Medicinal Chemistry Semaphorins and their Receptors in Stem and Cancer Cells
Current Medicinal Chemistry The Family B1 GPCR: Structural Aspects and Interaction with Accessory Proteins
Current Drug Targets