Proteomic profiling in MPTP monkey model for early Parkinson disease biomarker discovery

• Type of Material: Article
• Authors: Xiangmin Lin, University of Washington; Min Shi, University of Washington; Jeyaraj Gunasingh Masilamoni, Emory University; Romel Dator, University of Washington; James Movius, University of Washington; Patrick Aro, University of Washington; Yoland Smith, Emory University; Jing Zhang, University of Washington
• Language: English
• Date: 2015-07-01
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2015 Elsevier B.V. All rights reserved.
• Final Published Version (URL): http://dx.doi.org/10.1016/j.bbapap.2015.01.007
• Title of Journal or Parent Work: Biochimica et Biophysica Acta Proteins and Proteomics
• ISSN: 1388-1981
• Volume: 1854
• Issue: 7
• Start Page: 779
• End Page: 787
• Grant/Funding Information: It was also supported in part by the University of Washington’s Proteomics Resource (UWPR95794), a NIH infrastructure grant to the Yerkes National Primate Research Center (P51 OD011132), the Emory UDALL Center of Excellence for Parkinson’s Disease (P50 NS071669), and the National Natural Science Foundation of China (NSFC) projects (31200105 and 31470238).; This study was supported by generous grants from the National Institutes of Health (NIH) (R01 NS057567, U01 NS082137, P50 NS062684-6221, P30 ES007033-6364, R01 AG033398, R01 ES016873, and R01 ES019277 to JZ).
• Keywords: PROTEINS; Putamen; NEURONS; TREATED MONKEYS; Macaca mulatta; Phosphoproteomics; Science & Technology; Biophysics; Parkinson disease; GLYCOPROTEINS; QUANTIFICATION; Life Sciences & Biomedicine; Biochemistry & Molecular Biology; IDENTIFICATION; MASS-SPECTROMETRY; NEURODEGENERATIVE DISEASES; HUMAN CEREBROSPINAL-FLUID; Glycoproteomics; 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP); SUBSTANTIA-NIGRA
• Research Categories: Agriculture, Animal Pathology; Health Sciences, Pathology; Biology, Neuroscience

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.