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Proteomic Screen of Brain Glycoproteome Reveals Prion Specific Marker of Pathogenesis
Author(s) -
Lamoureux Lise,
Simon Sharon L.R.,
Waitt Brooks,
Knox J. David
Publication year - 2018
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.201700296
Subject(s) - biology , glial fibrillary acidic protein , proteome , astrogliosis , wheat germ agglutinin , scrapie , proteomics , pathology , western blot , progressive supranuclear palsy , neuroinflammation , microbiology and biotechnology , lectin , prion protein , disease , immunology , biochemistry , gene , neuroscience , central nervous system , medicine , immunohistochemistry , inflammation
Transmissible spongiform encephalopathies (TSEs) are neurodegenerative disorders caused by the presence of an infectious prion protein. The primary site of pathology is the brain characterized by neuroinflammation, astrogliosis, prion fibrils, and vacuolation. The events preceding the observed pathology remain in question. We sought to identify biomarkers in the brain of TSE‐infected and aged‐matched control mice using two‐dimensional fluorescence difference gel electrophoresis (2D‐DIGE). Since the brain proteome is too complex to resolve all proteins using 2D‐DIGE, protein samples are initially filtered through either concanavalin A (ConA) or wheat‐germ agglutinin (WGA) columns. Four differentially abundant proteins are identified through screening of the two different glycoproteomes: Neuronal growth regulator 1 (NEGR1), calponin‐3 (CNN3), peroxiredoxin‐6 (Prdx6), and glial fibrillary acidic protein (GFAP). Confirmatory Western blots are performed with samples from TSE‐infected and comparative Alzheimer's disease (AD) affected brains and their respective controls from time points throughout the disease courses. The abundance of three of the four proteins increases significantly during later stages of prion disease whereas NEGR1 decreases in abundance. Comparatively, no significant changes are observed in later stages of AD. Our lab is the first to associate the glycosylated NEGR1 protein with prion disease pathology.