Sulfated Polysaccharides Promote the Assembly of Amyloid beta1-42 Peptide into Stable Fibrils of Reduced Cytotoxicity Export

@article{Bravo_JBC08, 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, Abeta1-42. 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 Abeta1-42 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 Abeta1-42 species on Ca2+ homeostasis show that weakly structured nodular fibrils, but not CSB-induced smooth fibrils, trigger a rise in cytosolic Ca2+ that depends on the presence of both extracellular and intracellular stocks. In vitro assays indicate that such transient, local Ca2+ increases can have a direct effect in promoting the formation of Tau filaments similar to those isolated from Alzheimer disease brains. 10.1074/jbc.M709870200}, author = {Bravo, Ramona and Arimon, Muriel and Valle-Delgado, Juan J. and Garcia, Raquel and Durany, Nuria and Castel, Susanna and Cruz, Montserrat and Ventura, Salvador and Fernandez-Busquets, Xavier}, citeulike-article-id = {3514861}, citeulike-linkout-0 = {http://dx.doi.org/10.1074/jbc.M709870200}, citeulike-linkout-1 = {http://www.jbc.org/cgi/content/abstract/283/47/32471}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/18819917}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=18819917}, day = {21}, doi = {10.1074/jbc.M709870200}, journal = {Journal of Biological Chemistry}, keywords = {abeta, amyloid, cytotoxicity, sulfated-polysaccharide}, month = {November}, number = {47}, pages = {32471--32483}, posted-at = {2008-11-14 18:26:26}, priority = {2}, title = {Sulfated Polysaccharides Promote the Assembly of Amyloid beta1-42 Peptide into Stable Fibrils of Reduced Cytotoxicity}, url = {http://dx.doi.org/10.1074/jbc.M709870200}, volume = {283}, year = {2008} }

TY - JOUR ID - Bravo_JBC08 L3 - citeulike-article-id:3514861 N2 - 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, Abeta1-42. 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 Abeta1-42 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 Abeta1-42 species on Ca2+ homeostasis show that weakly structured nodular fibrils, but not CSB-induced smooth fibrils, trigger a rise in cytosolic Ca2+ that depends on the presence of both extracellular and intracellular stocks. In vitro assays indicate that such transient, local Ca2+ increases can have a direct effect in promoting the formation of Tau filaments similar to those isolated from Alzheimer disease brains. 10.1074/jbc.M709870200 IS - 47 JF - Journal of Biological Chemistry EP - 32483 TI - Sulfated Polysaccharides Promote the Assembly of Amyloid beta1-42 Peptide into Stable Fibrils of Reduced Cytotoxicity VL - 283 SP - 32471 KW - abeta KW - amyloid KW - cytotoxicity KW - sulfated-polysaccharide AU - Bravo, Ramona AU - Arimon, Muriel AU - Valle-Delgado, Juan AU - Garcia, Raquel AU - Durany, Nuria AU - Castel, Susanna AU - Cruz, Montserrat AU - Ventura, Salvador AU - Fernandez-Busquets, Xavier PY - 2008/11/21/ UR - http://dx.doi.org/10.1074/jbc.M709870200 ER -