Sulfonated dyes attenuate the toxic effects of beta-amyloid in a structure-specific fashion.
We recently reported that several sulfate-containing glycosaminoglycans, a class of compounds associated with the beta-amyloid plaques of Alzheimer's disease, attenuate the toxic effects of beta-amyloid fragments beta 25-35 and beta 1-40. The amyloid-binding sulfonated dye Congo Red was shown to have a similar effect. Using two clonal cell lines, we now demonstrate that several sulfonated dyes attenuate beta-amyloid toxicity and that the protective effect appears specific for compounds whose sulfonate groups can interact with the beta-pleated structure of aggregated amyloid. 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 / Q000009:adverse effects* / Q000037:antagonists & inhibitors* / Q000494:pharmacology / Q000633:toxicity; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004396:Coloring Agents / Q000737:chemistry / Q000494:pharmacology*; D003224:Congo Red / Q000737:chemistry / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D016716:PC12 Cells; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship; D013431:Sulfates / Q000737:chemistry / Q000494:pharmacology*
D016229:Amyloid beta-Peptides; D004396:Coloring Agents; D010446:Peptide Fragments; D013431:Sulfates; C078592:amyloid beta-protein (1-40); C074636:amyloid beta-protein (25-35); D003224:Congo Red