NDLI: Sulfated polysaccharides promote the assembly of amyloid beta(1-42) peptide into stable fibrils of reduced cytotoxicity.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Bravo, Ramona Arimon, Muriel Durany, Núria Valle-delgado, Juan José García, Raquel Castel, Susanna Cruz, Montserrat Ventura, Salvador Fernàndez-busquets, Xavier
Description	Author Affiliation: Bravo R ( Biomolecular Interactions Team, Nanobioengineering Group, Institute for Bioengineering of Catalonia, Barcelona Science Park, University of Barcelona, Baldiri Reixac 10, Barcelona E08028, Spain.)
Abstract	The histopathological hallmarks of Alzheimer disease are the self-aggregation of the amyloid beta peptide (Abeta) in extracellular amyloid fibrils and the formation of intraneuronal Tau filaments, but a convincing mechanism connecting both processes has yet to be provided. Here we show that the endogenous polysaccharide chondroitin sulfate B (CSB) promotes the formation of fibrillar structures of the 42-residue fragment, Abeta(1-42). Atomic force microscopy visualization, thioflavin T fluorescence, CD measurements, and cell viability assays indicate that CSB-induced fibrils are highly stable entities with abundant beta-sheet structure that have little toxicity for neuroblastoma cells. We propose a wedged cylinder model for Abeta(1-42) fibrils that is consistent with the majority of available data, it is an energetically favorable assembly that minimizes the exposure of hydrophobic areas, and it explains why fibrils do not grow in thickness. Fluorescence measurements of the effect of different Abeta(1-42) species on Ca(2+) homeostasis show that weakly structured nodular fibrils, but not CSB-induced smooth fibrils, trigger a rise in cytosolic Ca(2+) that depends on the presence of both extracellular and intracellular stocks. In vitro assays indicate that such transient, local Ca(2+) increases can have a direct effect in promoting the formation of Tau filaments similar to those isolated from Alzheimer disease brains.
ISSN	00219258
e-ISSN	1083351X
Journal	Journal of Biological Chemistry
Issue Number	47
Volume Number	283
Language	English
Publisher	American Society for Biochemistry and Molecular Biology (United States)
Publisher Date	2008-11-21
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Amyloid Beta-Peptides Chemistry Peptide Fragments Polysaccharides Metabolism Calcium Cell Line, Tumor Cell Survival Circular Dichroism Cytosol Microscopy, Atomic Force Peptides Protein Binding Protein Conformation Protein Structure, Secondary Thiazoles Tau Proteins Research Support, Non-U.S. Gov't Biochemistry Molecular Biology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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