The proteomic approach in Parkinson's disease

Parkinson's disease (PD) is a complex, multifactorial neurodegenerative disease affecting about 2% of the population over 65 years. Etiopathogenetic mechanisms of PD are not fully understood, although a number of factors contributing to the selective degeneration of substantia nigra neurons have been identified, including mitochondrial dysfunction, proteasomal impairment, oxidative stress, excitotoxicity, and inflammation. Although a global view of the disease at the molecular level can be obtained only from the biochemical analysis of the affected human tissue, difficulties in obtaining human specimens of the affected area have limited substantially the number of reports published to date. Therefore, cellular and animal models of the disease have been developed to investigate single factors contributing to disease pathogenesis, e.g., protein aggregation or altered dopamine homeostasis. In this review, we report how proteomic methodologies have been used so far to investigate cellular and animal models of PD, as well as to compare postmortem specimens of substantia nigra of affected patients to that of control subjects. Proteomic studies concur to highlight the role of a compromised antioxidant defense in PD pathogenesis. The proteomic approach in the investigation of etiopathogenetic mechanisms of PD is still at its beginning, however, the findings reviewed here should serve as a useful foundation to further work.