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Comparative Proteomic Profiling Identifies Reciprocal Expression of Mitochondrial Proteins Between White and Gray Matter Lesions From Multiple Sclerosis Brains

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 immunohis...

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Autores principales: Rai, Nagendra Kumar, Singh, Vaibhav, Li, Ling, Willard, Belinda, Tripathi, Ajai, Dutta, Ranjan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8740228/
https://www.ncbi.nlm.nih.gov/pubmed/35002930
http://dx.doi.org/10.3389/fneur.2021.779003
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author Rai, Nagendra Kumar
Singh, Vaibhav
Li, Ling
Willard, Belinda
Tripathi, Ajai
Dutta, Ranjan
author_facet Rai, Nagendra Kumar
Singh, Vaibhav
Li, Ling
Willard, Belinda
Tripathi, Ajai
Dutta, Ranjan
author_sort Rai, Nagendra Kumar
collection PubMed
description 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.
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spelling pubmed-87402282022-01-08 Comparative Proteomic Profiling Identifies Reciprocal Expression of Mitochondrial Proteins Between White and Gray Matter Lesions From Multiple Sclerosis Brains Rai, Nagendra Kumar Singh, Vaibhav Li, Ling Willard, Belinda Tripathi, Ajai Dutta, Ranjan Front Neurol Neurology 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. Frontiers Media S.A. 2021-12-24 /pmc/articles/PMC8740228/ /pubmed/35002930 http://dx.doi.org/10.3389/fneur.2021.779003 Text en Copyright © 2021 Rai, Singh, Li, Willard, Tripathi and Dutta. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neurology
Rai, Nagendra Kumar
Singh, Vaibhav
Li, Ling
Willard, Belinda
Tripathi, Ajai
Dutta, Ranjan
Comparative Proteomic Profiling Identifies Reciprocal Expression of Mitochondrial Proteins Between White and Gray Matter Lesions From Multiple Sclerosis Brains
title Comparative Proteomic Profiling Identifies Reciprocal Expression of Mitochondrial Proteins Between White and Gray Matter Lesions From Multiple Sclerosis Brains
title_full Comparative Proteomic Profiling Identifies Reciprocal Expression of Mitochondrial Proteins Between White and Gray Matter Lesions From Multiple Sclerosis Brains
title_fullStr Comparative Proteomic Profiling Identifies Reciprocal Expression of Mitochondrial Proteins Between White and Gray Matter Lesions From Multiple Sclerosis Brains
title_full_unstemmed Comparative Proteomic Profiling Identifies Reciprocal Expression of Mitochondrial Proteins Between White and Gray Matter Lesions From Multiple Sclerosis Brains
title_short Comparative Proteomic Profiling Identifies Reciprocal Expression of Mitochondrial Proteins Between White and Gray Matter Lesions From Multiple Sclerosis Brains
title_sort comparative proteomic profiling identifies reciprocal expression of mitochondrial proteins between white and gray matter lesions from multiple sclerosis brains
topic Neurology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8740228/
https://www.ncbi.nlm.nih.gov/pubmed/35002930
http://dx.doi.org/10.3389/fneur.2021.779003
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