Polyhydroxylated C-60, fullerenols, as glutamate receptor antagonists and neuroprotective agents

Derivatives of C-60 have been shown to be effective free radical scavengers . Hence, many of the biological functions of fullerene are believed to be d ue to their antioxidant properties. Here we present evidence to show that f ullerenols, that are caged fullerene oxides, exert their neuroprotective fu nctions by blocking glutamate receptors and lowering the intracellular calc ium, [Ca2+](i). In neuronal cultures, fullerenols reduce glutamate-induced neurotoxicity by about 80% at 50 muM. No significant effect was observed on H2O2/Fe2+-induced neurotoxicity under the same conditions. Fullerenols wer e found to inhibit glutamate receptor binding in a dose-dependent manner in hibiting 50% of glutamate binding at 50 muM. Furthermore, AMPA receptors we re found to be more sensitive to fullerenols than NMDA and KA receptors. On the other hand, GABA(A) receptors and taurine receptors were not significa ntly affected by fullerenols at the same concentrations used, suggesting th at fullerenols inhibit primarily the glutamate receptors. In addition, full erenols were also found to lower glutamate (Glu) receptor-induced elevation of [Ca2+](i), suggesting that the underlying mechanism of neuronal protect ive function of fullerenols is likely due to its ability to block the gluta mate receptors and to reduce the level of [Ca2+](i). (C) 2000 Wiley-Liss, I nc.