Journal
CURRENT ALZHEIMER RESEARCH
Volume 7, Issue 5, Pages 428-438Publisher
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/156720510791383787
Keywords
Alzheimer's disease; advanced glycation endproducts; amyloid fibrils; amyloid beta peptide; apoptosis; carbohydrates; glycosaminoglycans
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Funding
- Ministerio de Ciencia y Tecnologia, Spain [BIO2002-00128, BIO2005-01591, BIO2008-01184, CSD2006-00012]
- FEDER
- Generalitat de Catalunya [2005SGR-270, 2009SGR-760]
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One mechanism leading to neurodegeneration during Alzheimer's Disease (AD) is amyloid beta peptide (A beta)-induced neurotoxicity. Among the factors proposed to potentiate A beta 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 A beta in primary neuronal cultures. Pretreatment of the 42-residue A beta fragment (A beta(1-42)) with the ubiquitous brain carbohydrates, glucose, fructose, and the GAG chondroitin sulfate B (CSB) inhibits A beta beta(1-42)-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 A beta 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 A beta(1-42) toxicity through different mechanisms both dependent and independent of AGE formation.
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