Proteomics in human Parkinson's disease research

• Published in: Journal of proteomics Vol. 73; no. 1; pp. 10 - 29
• Main Authors: Licker, Virginie, Kövari, Enikö, Hochstrasser, Denis F., Burkhard, Pierre R.
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier B.V 02.11.2009; Elsevier
• Subjects: Biological and medical sciences; Biomedical Research - trends; Brain - metabolism; Brain - pathology; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Disease Progression; Diverse techniques; Fundamental and applied biological sciences. Psychology; Humans; Lewy Bodies - metabolism; Lewy Bodies - pathology; Lewy body; Medical sciences; Molecular and cellular biology; Nerve Degeneration - etiology; Nerve Degeneration - metabolism; Neurology; Parkinson Disease - cerebrospinal fluid; Parkinson Disease - etiology; Parkinson Disease - metabolism; Parkinson Disease - pathology; Parkinson's disease; Protein; Protein Processing, Post-Translational - physiology; Proteome - analysis; Proteomics; Proteomics - methods; Substantia nigra; α-synuclein; LN; VTA; Parkinson's disease; LP; Substantia nigra; ALS; CNS; UB; DUB; α-SYN; CSF; UPS; α-synuclein; AD; SNpc; 2-DE; Protein; PTMs; PD; LB; LC; LCM; ROS; Proteomics; LD; TMT; MPTP; DA; HE; NM; Lewy body; Human; Alpha synuclein; Parkinson disease
• ISSN: 1874-3919; 1876-7737
• DOI: 10.1016/j.jprot.2009.07.007

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.