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

Abstract

In this review, we report how proteomic methodologies have been used to investigate cellular and animal models of Parkinson’s disease (PD), with a special focus on α-synuclein. PD is a complex, multifactorial neurodegenerative disease affecting approximately 2% of the population over 65 years of age, pathologically characterized by α-synuclein intraneuronal inclusions. 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. Therefore, cellular and animal models of the disease have been developed to investigate single factors contributing to disease pathogenesis; for example, α-synuclein aggregation and altered dopamine homeostasis. Proteomic studies on cellular and animal models have not only confirmed existing theories on PD pathogenesis (mitochondrial impairment, oxidative stress, failure of the ubiquitine–proteasome system), but also allowed the discovery of new important common features of presymptomatic (or premotor) stages of PD, such as dysregulation of cytoskeletal proteins that could be involved at the origin of the disorder.

Keywords::

• α-synuclein
• animal model
• brain proteomics
• cellular model
• Parkinson’s disease

Acknowledgements

This review is dedicated to the memory of Professor Bruno Bergamasco. His contribution to understanding the functional role of the iron-neuromelanin system first, and the biochemical mechanisms underlying neurodegeneration in Parkinson’s disease using proteomics in more recent times will always be appreciated and remembered by his many friends and colleagues.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.