HEPARAN-SULFATE AND CHONDROITIN SULFATE GLYCOSAMINOGLYCAN ATTENUATE BETA-AMYLOID(25-35) INDUCED NEURODEGENERATION IN CULTURED HIPPOCAMPAL-NEURONS

beta-Amyloid peptide has been reported to be toxic to neurons in vitro and in vivo. The fragment of the beta 1-42 peptide believed to be res ponsible for this toxicity consists of amino acids 25 to 35. beta-Amyl oid protein, heparan sulfate (HS) glycosaminoglycan (GAG), and proteog lycan (PG) are all localized throughout the senile plaques found in Al zheimer's disease. Chondroitin sulfate (CS) and dermatan sulfate have also been found at the periphery of senile plaques. We have found that both HS and CS prevented neurite fragmentation and toxicity normally induced by beta 25-35. HS and CS by themselves did not have a signific ant influence on cell viability, indicating that their protective acti ons were not due to a general trophic effect. In contrast, cultures tr eated with HS and beta 1-42 did not show significantly reduced toxicit y compared to cultures treated with beta 1-42 alone despite specific b inding interactions. These data indicate that one function of GAGs in the brain may be to protect neurons from select toxic insults and inju ry, and additionally suggest that HS interacts differently with differ ent beta-amyloid fragments. These data further suggest that different beta-amyloid fragments may induce distinct mechanisms of toxicity in v itro.