Sulfated glycosaminoglycans and dyes attenuate the neurotoxic effects of beta-amyloid in rat PC12 cells.
Glycosaminoglycan (GAG)-containing proteoglycans are associated with the neuritic plaques and cerebrovascular beta-amyloid deposits of Alzheimer's disease as well as with the amyloid deposits of prion and other disorders. GAGs and other sulfate-containing compounds have previously been shown to bind beta-amyloid peptide in vitro, suggesting possible effects of beta-amyloid deposition and/or toxicity in vivo. Using reduction of the redox dye 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) to measure beta-amyloid neurotoxicity in rat pheochromocytoma PC12 cells, several polysulfated GAGs and synthetic sulfate-containing compounds were found to attenuate the neurotoxic effects of beta-amyloid fragments beta 25-35 and beta 1-40. These results suggest that by binding beta-amyloid these compounds may prevent toxic interactions of the peptide with cells.
Pollack
S J
SJ
Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex, UK.
Sadler
I I
II
Hawtin
S R
SR
Tailor
V J
VJ
Shearman
M S
MS
D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000633:toxicity; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004396:Coloring Agents / Q000494:pharmacology*; D006025:Glycosaminoglycans / Q000494:pharmacology*; D010084:Oxidation-Reduction; D016716:PC12 Cells; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000633:toxicity; D051381:Rats; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology
D016229:Amyloid beta-Peptides; D004396:Coloring Agents; D006025:Glycosaminoglycans; D010446:Peptide Fragments; D013778:Tetrazolium Salts; D013844:Thiazoles; C078592:amyloid beta-protein (1-40); C074636:amyloid beta-protein (25-35); C022616:thiazolyl blue