Chrysamine-G, a lipophilic analogue of congo red, inhibits Aβ-induced toxicity in PC12 cells

Abstract

Increasing evidence suggests that deposition of amyloid-beta (Aβ) peptide leads to neurodegeneration in Alzheimer's disease. Congo red, a histologic dye that binds to amyloid has previously been shown to diminish the toxic effects of Aβ in cell culture. Since Congo red is too highly charged to enter the brain in significant quantities, a lipophilic derivative, Chrysamine-G, was tested for the ability to attenuate Aβ[25–35]-induced toxicity in PC12 cells using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Chrysamine-G showed a concentration-dependent inhibition of Aβ[25–35]-induced toxicity. This protective effect became significant at 0.2 μM, a concentration very close to the K_i for Chrysamine-G binding to synthetic Aβ (0.37 μM). A decarboxy derivative of Chrysamine-G, which does not bind to Aβ, also did not protect against Aβ-induced toxicity. The protective effects of Chrysamine-G may relate to its ability to bind directly to Aβ and may involve other post-binding effects as well.