Curcumin, the major yellow pigment in turmeric (Curcuma longa), is a well-documented naturally-occurring anti-oxidant with numerous pharmacological activities such as anti-inflammatory, anti-carcinogenic and anti-bacterial effects. In this study, curcumin's neuroprotective effect was carefully examined using a coculture system, based on reports that curcumin-containing plants are neuroprotective. Coculturing neuronal cells and activated microglial cells enhanced dopamine-induced neuronal cell death from 30% up to 50%. However, curcumin did not protect dopamine-directed neuronal cell death and sodium nitroprosside (SNP)-induced NO generation, but only blocked activated microglial cell-mediated neuronal cell damage under inflammatory conditions. Indeed, curcumin blocked the production of pro-inflammatory and cytotoxic mediators such as NO, TNF-alpha, IL-1alpha, and IL-6 produced from Abeta(25-35)/IFN-gamma- and LPS-stimulated microglia, in a dose-dependent manner. Therefore, our results suggest that curcumin-mediated neuroprotective effects may be mostly due to its anti-inflammatory effects.