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Comparative proteomic profiling identifies reciprocal expression of mitochondrial proteins between white and grey matter lesions from multiple sclerosis brains

ABSTRACT: Multiple Sclerosis (MS) is a chronic inflammatory and demyelinating disease of the central nervous system (CNS), where ongoing demyelination and remyelination failure are the major factors for progressive neurological disability. In this report, we employed a comprehensive proteomic approach and immunohistochemical (IHC) validation to gaininsight into the pathobiological mechanisms that may be associated with the progressive phase of MS disease. Isolated proteins from myelinated regions, demyelinated white matter lesions (WMLs), and grey-matter lesions (GMLs) of well-characterized progressive MS brain tissues were subjected to label-free quantitative mass spectrometry (LFQ-MS). Using a system-biology approach, we detected increased expression of proteins belonging to mitochondrial electron transport complexes and oxidative phosphorylatio pathway in WMLs. Intriguingly, many of these proteins and pathways had opposite expression patterns in GMLs of progressive MS brains. A comparison to the huma MitoCarta database mapped the mitochondrial proteins to mitochondrial subunits in both WMLs and GMLs. Taken together, we provide evidence of opposite expression of mitochondrial proteins in response to demyelination of white- and grey-matter regions in progressive MS brain.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Brain

DISEASE(S): Multiple Sclerosis

SUBMITTER: Ling Li

LAB HEAD: Ranjan Dutta

PROVIDER: PXD029285 | Pride | 2021-12-21

REPOSITORIES: Pride

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