Neoechinulin A, an alkaloid from Eurotium rubrum, can protect neuronal PC12 cells against cytotoxicity of a potent oxidant, peroxynitrite. Because involvement of peroxynitrite has been suggested in the pathogenesis of Parkinson's disease, we assessed whether this alkaloid could also protect PC12 cells from the cytocidal action of 1-methyl-4-phenylpyridine (MPP+), a neurotoxin capable of provoking acute Parkinson's-like neurodegeneration in humans. Neoechinulin A could protect PC12 cells from MPP+ cytotoxicity without protecting against mitochondrial complex I dysfunction, suggesting the alkaloid can ameliorate downstream events of mitochondrial failure. Thus, neoechinulin A has the potential to intervene in this progressive neurodegeneration.