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Biochim Biophys Acta. 2015 Jul;1854(7):779-87. doi: 10.1016/j.bbapap.2015.01.007. Epub 2015 Jan 22.

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

Author information

1
Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA; School of Life Sciences, Fujian Agricultural and Forestry University, Fuzhou, Fujian, China.
2
Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA.
3
Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
4
Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA; Department of Neurology, Emory University, Atlanta, GA, USA.
5
Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA. Electronic address: zhangj@uw.edu.

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.

KEYWORDS:

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP); Glycoproteomics; Macaca mulatta; Parkinson disease; Phosphoproteomics; Putamen

PMID:
25617661
PMCID:
PMC4760626
DOI:
10.1016/j.bbapap.2015.01.007
[Indexed for MEDLINE]
Free PMC Article

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