Citation

Mallah K, Quanico J, Raffo-Romero A, Cardon T, Aboulouard S, Devos D, Kobeissy F, Zibara K, Salzet M, Fournier I. Mol. Cell Proteomics 2019; 18(8): 1669-1682.

Affiliation

Université de Lille, INSERM, U1192 - Laboratoire Protéomique, Réponse Inflammatoire et Spectrométrie de Masse (PRISM), France.

Copyright

(Copyright © 2019, American Society for Biochemistry and Molecular Biology)

DOI

10.1074/mcp.RA119.001604

PMID

31204315

Abstract

Traumatic brain injury (TBI) represents a major health concerns with no clinically-approved FDA drug available for therapeutic intervention. Several genomics and neuroproteomics studies have been employed to decipher the underlying pathological mechanisms involved that can serve as potential neurotherapeutic targets and unveil a possible underlying relation of TBI to other secondary neurological disorders. In this work, we present a novel high throughput systems biology approach using a spatially-resolved microproteomics platform conducted on different brain regions in an experimental rat model of moderate of controlled cortical injury (CCI) at a temporal pattern post-injury (1 day, 3 days, 7 days, and 10 days). Mapping the spatiotemporal landscape of signature markers in TBI revealed an overexpression of major protein families known to be implicated in Parkinson's disease (PD) such as GPR158, HGMB1, Synaptotagmin and Glutamate Decarboxylase in the ipsilateral substantia nigra. In silico bioinformatics docking experiments indicated the potential correlation between TBI and PD through alpha-synuclein. In an in vitro model, stimulation with palmitoylcarnitine triggered an inflammatory response in macrophages and a regeneration processes in astrocytes which also further conformed confirmed the in vivo TBI proteomics data. Taken together, this is the first study to assess the microproteomics landscape in TBI, mainly in the substantia nigra, thus revealing a potential predisposition for PD or Parkinsonism post-TBI.

Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

Language: en

Keywords

Imaging; Label-free quantification; Lipidomics; Long chain Acylcarnitines; MALDI Mass spectrometry imaging; Mass Spectrometry; Parkinson's disease; Spatially-Resolved Microproteomics; Spatio-Temporal; Systems biology*; Traumatic Brain Injury