Proteomics; applications in familial Parkinson's disease.

Our understanding of the biological basis of Parkinson's disease (PD) has been greatly improved in recent years by the identification of mutations that lead to inherited PD. One of the strengths of using genetics to try to understand disease biology is that it is inherently unbiased and can be applied at a genome-wide scale. More recently, many studies have used another set of unbiased approaches, proteomics, to query the function of familial PD genes in a variety of contexts. We will discuss some specific examples, including; elucidation of protein-protein interaction networks for two dominantly inherited genes, α-synuclein and leucine rich-repeat kinase 2 (LRRK2); the identification of substrates for three genes for familial PD that are also enzymes, namely LRRK2, pink1, and parkin; and changes in protein abundance that arise downstream to introduction of mutations associated with familial PD. We will also discuss those situations where we can integrate multiple proteomics approaches to nominate deeper networks of inter-related events that outline pathways relevant to inherited PD. This article is part of the Special Issue "Proteomics". © Published 2019. This article is a U.S. Government work and is in the public domain in the USA.