title: Proteomic profiling in MPTP monkey model for early Parkinson disease biomarker discovery.
abstract: Identification of reliable and robust biomarkers is crucial to enable early diagnosis of Parkinson disease (PD) and monitoring disease progression. While imperfect, the slow, chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced non-human primate animal model system of parkinsonism is an abundant source of pre-motor or early stage PD biomarker discovery. Here, we present a study of a MPTP rhesus monkey model of PD that utilizes complementary quantitative iTRAQ-based proteomic, glycoproteomics and phosphoproteomics approaches. We compared the glycoprotein, non-glycoprotein, and phosphoprotein profiles in the putamen of asymptomatic and symptomatic MPTP-treated monkeys as well as saline injected controls. We identified 86 glycoproteins, 163 non-glycoproteins, and 71 phosphoproteins differentially expressed in the MPTP-treated groups. Functional analysis of the data sets inferred the biological processes and pathways that link to neurodegeneration in PD and related disorders. Several potential biomarkers identified in this study have already been translated for their usefulness in PD diagnosis in human subjects and further validation investigations are currently under way. In addition to providing potential early PD biomarkers, this comprehensive quantitative proteomic study may also shed insights regarding the mechanisms underlying early PD development. This article is part of a Special Issue entitled: Neuroproteomics: Applications in neuroscience and neurology.
authors.affiliation: Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA; School of Life Sciences, Fujian Agricultural and Forestry University, Fuzhou, Fujian, China.
authors.forename: Xiangmin
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Shi
authors.affiliation: Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
authors.forename: Jeyaraj Gunasingh
authors.initials: JG
authors.lastname: Masilamoni
authors.affiliation: Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA.
authors.forename: Romel
authors.initials: R
authors.lastname: Dator
authors.affiliation: Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA.
authors.forename: James
authors.initials: J
authors.lastname: Movius
authors.affiliation: Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Aro
authors.affiliation: Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA; Department of Neurology, Emory University, Atlanta, GA, USA.
authors.forename: Yoland
authors.initials: Y
authors.lastname: Smith
authors.affiliation: Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA. Electronic address: zhangj@uw.edu.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D020267:MPTP Poisoning / Q000378:metabolism*; D008253:Macaca mulatta; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D040901:Proteomics
chemical_list: D015415:Biomarkers; D006023:Glycoproteins; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins
keywords: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP); Glycoproteomics; Macaca mulatta; Parkinson disease; Phosphoproteomics; Putamen