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.
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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 |
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