AUTHOR=Rai Nagendra Kumar , Singh Vaibhav , Li Ling , Willard Belinda , Tripathi Ajai , Dutta Ranjan TITLE=Comparative Proteomic Profiling Identifies Reciprocal Expression of Mitochondrial Proteins Between White and Gray Matter Lesions From Multiple Sclerosis Brains JOURNAL=Frontiers in Neurology VOLUME=12 YEAR=2021 URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2021.779003 DOI=10.3389/fneur.2021.779003 ISSN=1664-2295 ABSTRACT=

Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of the central nervous system, 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 validation to gain insight into the pathobiological mechanisms that may be associated with the progressive phase of MS. Isolated proteins from myelinated regions, demyelinated white-matter lesions (WMLs), and gray-matter lesions (GMLs) from well-characterized progressive MS brain tissues were subjected to label-free quantitative mass spectrometry. Using a system-biology approach, we detected increased expression of proteins belonging to mitochondrial electron transport complexes and oxidative phosphorylation pathway in WMLs. Intriguingly, many of these proteins and pathways had opposite expression patterns and were downregulated in GMLs of progressive MS brains. A comparison to the human 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 gray-matter regions in progressive MS brain.