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 responsible for this toxicity consists of amino acids 25 to 35. beta-amyloid protein, heparan sulfate (HS) glycosaminoglycan (GAG), and proteoglycan (PG) are all localized throughout the senile plaques found in Alzheimer'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 significant influence on cell viability, indicating that their protective actions were not due to a general trophic effect. In contrast, cultures treated with HS and beta 1-42 did not show significantly reduced toxicity compared to cultures treated with beta 1-42 alone despite specific binding interactions. These data indicate that one function of GAGs in the brain may be to protect neurons from select toxic insults and injury, and additionally suggest that HS interacts differently with different beta-amyloid fragments. These data further suggest that different beta-amyloid fragments may induce distinct mechanisms of toxicity in vitro.
Woods
A G
AG
Department of Psychobiology, University of California, Irvine 92717-4550, USA.
Cribbs
D H
DH
Whittemore
E R
ER
Cotman
C W
CW
D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002809:Chondroitin Sulfates / Q000494:pharmacology*; D006497:Heparan Sulfate / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D009410:Nerve Degeneration / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects*; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D016229:Amyloid beta-Peptides; D002809:Chondroitin Sulfates; D006497:Heparan Sulfate; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); C074636:amyloid beta-protein (25-35); C038142:chondroitin sulfate glycosaminoglycan