The proteomic approach in Parkinson's disease

Abstract

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.

α-synuclein and Parkinson’s disease: a proteomic view

“…Although the proteomic approach in neuroscience research is very recent, several papers have been published in the last 4 years on the investigation of pathogenetic mechanisms of neurodegenerative disorders by proteomics [68][69][70]. Nevertheless, a small number of reports dealt with the proteomic investigation of human SNpc tissue [20,[71][72][73][74][75].…”

“…Currently, a few studies have been reported examining animal models of PD using proteomics [68][69][70]. To date, most information regarding the mechanisms involved in the pathogenesis of PD has gained from the study of transgenic animal models.…”

Proteomic analysis of dopamine and α‐synuclein interplay in a cellular model of Parkinson’s disease pathogenesis

“…In the present study, we investigate the dopamine effect on the expression pattern of cellular proteins in the human catecholaminergic neuroblastoma cell line SH‐SY5Y, overexpressing α‐synuclein. A proteomic analysis is expected to identify cellular alterations that are associated with dopamine treatment and modulated by α‐synuclein overexpression, without any a priori hypothesis [4,11,12]. SH‐SY5Y cells couple good dopamine transporter activity with a low activity of the vesicular monoamine transporter type 2, such that cytoplasmic dopamine concentration may be raised by the administration of exogenous dopamine in the culture medium [7,13–15].…”

Development of a Highly Efficient 2-D System with a Serially Coupled Long Column and Its Application in Identification of Rat Brain Integral Membrane Proteins with Ionic Liquids-Assisted Solubilization and Digestion

“…Parkinson’s disease (PD) is a complex, multifactorial neurodegenerative disease affecting about 3% of the population over 65 years. − It is often characterized by a gradual degeneration of dopaminergic neurons in the midbrain substantia nigra pars compacta (SNc). , The proteins identified in brain may be related with PD, based on the reference reported …”