Parkinson's disease (PD) is associated with neurodegeneration of the nigrostriatal tract and is accompanied with loss of tyrosine hydroxylase (TH) and dopamine (DA). Development of neuroprotective strategies targeting PD is often undermined by lack of proper understanding of processes contributing to the pathology. In this mini review we have tried to briefly outline the involvement of TH and α-synuclein in PD. Aberrant expression of α-synuclein is toxic to dopaminergic neurons. It interacts with ubiquitin-proteasomal processing system, implicated in oxidative injury and mitochondrial dysfunction which ultimately induce neurodegenration and cell death. The contributions of DJ-1 in TH regulation have also been discussed. Brain specific TH expression with the combined use of the pegylated immunoliposome (PILs) gene transfer technology and brain specific promoters as a new approach to treat PD has also been included.