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Proteomics in human Parkinson's disease research
Affiliation:1. Oxford Parkinson''s Disease Centre, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK;2. Biogen, Cambridge, MA, USA;3. Medical Research Council Brain Network Dynamics Unit, University of Oxford, Oxford, UK;4. James Martin Stem Cell Facility, Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.;5. Institute of Neurogenetics, University of Leubeck, Maria-Goeppert-Str. 1, 23562 Luebeck, Germany.;6. Oxford Parkinson''s Disease Centre (OPDC), Oxford, UK
Abstract:During the last decades, considerable advances in the understanding of specific mechanisms underlying neurodegeneration in Parkinson's disease have been achieved, yet neither definite etiology nor unifying sequence of molecular events has been formally established. Current unmet needs in Parkinson's disease research include exploring new hypotheses regarding disease susceptibility, occurrence and progression, identifying reliable diagnostic, prognostic and therapeutic biomarkers, and translating basic research into appropriate disease-modifying strategies. The most popular view proposes that Parkinson's disease results from the complex interplay between genetic and environmental factors and mechanisms believed to be at work include oxidative stress, mitochondrial dysfunction, excitotoxicity, iron deposition and inflammation. More recently, a plethora of data has accumulated pinpointing an abnormal processing of the neuronal protein α-synuclein as a pivotal mechanism leading to aggregation, inclusions formation and degeneration. This protein-oriented scenario logically opens the door to the application of proteomic strategies to this field of research. We here review the current literature on proteomics applied to Parkinson's disease research, with particular emphasis on pathogenesis of sporadic Parkinson's disease in humans. We propose the view that Parkinson's disease may be an acquired or genetically-determined brain proteinopathy involving an abnormal processing of several, rather than individual neuronal proteins, and discuss some pre-analytical and analytical developments in proteomics that may help in verifying this concept.
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