Mutations in the parkin gene are currently thought to be the most common cause of familial Parkinsonism.Overexpression of parkin has been reported to prevent neuronal degeneration under various conditions.We generated a transgenic mouse model in which expression of wild type parkin was driven by neuron specific enolase promoter.Parkin transgenic mice exhibited less reduction of striatal TH protein and number of TH positive neurons in the substantia nigra induced by 1-Methyl-4-Phenyl-l,2,3,6-Tetrahydropyridine (MPTP).Such a phenomenon was especially more obvious in old transgenic mice.MPTP-induced mitochondrial impairment in the substantia nigra pars compacta was improved in parkin transgenic mice accompanied by elevated transcriptional expression of bcl-2 and D J-1.Decreased striatal α-synuclein accumulation was shown in old parkin transgenic mice, however, striatal Hsp70 expression revealed no significant changes within groups in both young and old mice.These results provide the first mammalian genetic evidence that overexpression ofparkin may attenuate dopaminergic neurodegeneration induced by MPTP through protection of mitochondria and reduction of α-synuclein in the nigrostriatal pathway.