Recently, it has been shown that release of cytochrome c from the mitochondria to the cytosol is required for activation of the caspase-3-dependent cascade in apoptosis, and also for α-synuclein aggregation. In the present study, we examined the effects of talipexole and pramipexole on the release of cytochrome c and α-synuclein, their aggregations, and activation of caspases. Treatment of human neuroblastoma SH-SY5Y cells with 1-methyl-4-phenylpyridinium (MPP + , 1 mM) induced the first event, which was the release of cytochrome c from the organellar fraction to the cytosolic fraction, then came the DNA fragmentation, and caused the last event, which was the accumulation of α-synuclein protein in the cytosolic fraction. Talipexole and pramipexole at low concentration (0.1–1 mM) significantly inhibited the accumulation of cytochrome c or α-synuclein in the cytosolic fraction. These drugs at high concentration (3–10 mM) inhibited in vitro aggregation of cytochrome c by hydrogen peroxide or that of α-synuclein by cytochrome c and hydrogen peroxide. In addition, in vitro activation of caspase-3 induced by cytochrome c and/or dATP was also inhibited by drugs at high concentration (5–10 mM). These results suggest that talipexole and pramipexole may have protective effects against the neurodegeneration, which is induced by intracellular accumulation of cytochrome c and α-synuclein.