CHRYSAMINE-G, A LIPOPHILIC ANALOG OF CONGO RED, INHIBITS A-BETA-INDUCED TOXICITY IN PC12 CELLS

Increasing evidence suggests that deposition of amyloid-beta (A beta) peptide leads to neurodegeneration in Alzheimer's disease. Congo red, a histologic dye that binds to amyloid has previously been shown to di minish the toxic effects of A beta in cell culture. Since Congo red is too highly charged to enter the brain in significant quantities, a li pophilic derivative, Chrysamine-G, was tested for the ability to atten uate A beta[25-35]-induced toxicity in PC12 cells using the (4,5-dimet hylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Chrysami ne-G showed a concentration-dependent inhibition of A beta[25-35]-indu ced toxicity. This protective effect became significant at 0.2 mu M, a concentration very close to the K-i for Chrysamine-G binding to synth etic A beta (0.37 mu M). A decarboxy derivative of Chrysamine-G, which does not bind to A beta, also did not protect against A beta-induced toxicity. The protective effects of Chrysamine-G may relate to its abi lity to bind directly to A beta and may involve other post-binding eff ects as well.