Cuprizone and EAE mouse frontal cortex proteomics revealed proteins altered in multiple sclerosis

Abstract Two pathophysiological different experimental models for multiple sclerosis were analyzed in parallel using quantitative proteomics in attempts to discover protein alterations applicable as diagnostic-, prognostic-, or treatment targets in human disease. The cuprizone model reflects de- and...

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Autores principales:	Eystein Oveland, Intakhar Ahmad, Ragnhild Reehorst Lereim, Ann Cathrine Kroksveen, Harald Barsnes, Astrid Guldbrandsen, Kjell-Morten Myhr, Lars Bø, Frode S. Berven, Stig Wergeland
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/84b83fd96e1d4449be897044b5da5617
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spelling	oai:doaj.org-article:84b83fd96e1d4449be897044b5da56172021-12-02T18:17:41ZCuprizone and EAE mouse frontal cortex proteomics revealed proteins altered in multiple sclerosis10.1038/s41598-021-86191-52045-2322https://doaj.org/article/84b83fd96e1d4449be897044b5da56172021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-86191-5https://doaj.org/toc/2045-2322Abstract Two pathophysiological different experimental models for multiple sclerosis were analyzed in parallel using quantitative proteomics in attempts to discover protein alterations applicable as diagnostic-, prognostic-, or treatment targets in human disease. The cuprizone model reflects de- and remyelination in multiple sclerosis, and the experimental autoimmune encephalomyelitis (EAE, MOG1-125) immune-mediated events. The frontal cortex, peripheral to severely inflicted areas in the CNS, was dissected and analyzed. The frontal cortex had previously not been characterized by proteomics at different disease stages, and novel protein alterations involved in protecting healthy tissue and assisting repair of inflicted areas might be discovered. Using TMT-labelling and mass spectrometry, 1871 of the proteins quantified overlapped between the two experimental models, and the fold change compared to controls was verified using label-free proteomics. Few similarities in frontal cortex between the two disease models were observed when regulated proteins and signaling pathways were compared. Legumain and C1Q complement proteins were among the most upregulated proteins in cuprizone and hemopexin in the EAE model. Immunohistochemistry showed that legumain expression in post-mortem multiple sclerosis brain tissue (n = 19) was significantly higher in the center and at the edge of white matter active and chronic active lesions. Legumain was associated with increased lesion activity and might be valuable as a drug target using specific inhibitors as already suggested for Parkinson’s and Alzheimer’s disease. Cerebrospinal fluid levels of legumain, C1q and hemopexin were not significantly different between multiple sclerosis patients, other neurological diseases, or healthy controls.Eystein OvelandIntakhar AhmadRagnhild Reehorst LereimAnn Cathrine KroksveenHarald BarsnesAstrid GuldbrandsenKjell-Morten MyhrLars BøFrode S. BervenStig WergelandNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Eystein Oveland Intakhar Ahmad Ragnhild Reehorst Lereim Ann Cathrine Kroksveen Harald Barsnes Astrid Guldbrandsen Kjell-Morten Myhr Lars Bø Frode S. Berven Stig Wergeland Cuprizone and EAE mouse frontal cortex proteomics revealed proteins altered in multiple sclerosis
description	Abstract Two pathophysiological different experimental models for multiple sclerosis were analyzed in parallel using quantitative proteomics in attempts to discover protein alterations applicable as diagnostic-, prognostic-, or treatment targets in human disease. The cuprizone model reflects de- and remyelination in multiple sclerosis, and the experimental autoimmune encephalomyelitis (EAE, MOG1-125) immune-mediated events. The frontal cortex, peripheral to severely inflicted areas in the CNS, was dissected and analyzed. The frontal cortex had previously not been characterized by proteomics at different disease stages, and novel protein alterations involved in protecting healthy tissue and assisting repair of inflicted areas might be discovered. Using TMT-labelling and mass spectrometry, 1871 of the proteins quantified overlapped between the two experimental models, and the fold change compared to controls was verified using label-free proteomics. Few similarities in frontal cortex between the two disease models were observed when regulated proteins and signaling pathways were compared. Legumain and C1Q complement proteins were among the most upregulated proteins in cuprizone and hemopexin in the EAE model. Immunohistochemistry showed that legumain expression in post-mortem multiple sclerosis brain tissue (n = 19) was significantly higher in the center and at the edge of white matter active and chronic active lesions. Legumain was associated with increased lesion activity and might be valuable as a drug target using specific inhibitors as already suggested for Parkinson’s and Alzheimer’s disease. Cerebrospinal fluid levels of legumain, C1q and hemopexin were not significantly different between multiple sclerosis patients, other neurological diseases, or healthy controls.
format	article
author	Eystein Oveland Intakhar Ahmad Ragnhild Reehorst Lereim Ann Cathrine Kroksveen Harald Barsnes Astrid Guldbrandsen Kjell-Morten Myhr Lars Bø Frode S. Berven Stig Wergeland
author_facet	Eystein Oveland Intakhar Ahmad Ragnhild Reehorst Lereim Ann Cathrine Kroksveen Harald Barsnes Astrid Guldbrandsen Kjell-Morten Myhr Lars Bø Frode S. Berven Stig Wergeland
author_sort	Eystein Oveland
title	Cuprizone and EAE mouse frontal cortex proteomics revealed proteins altered in multiple sclerosis
title_short	Cuprizone and EAE mouse frontal cortex proteomics revealed proteins altered in multiple sclerosis
title_full	Cuprizone and EAE mouse frontal cortex proteomics revealed proteins altered in multiple sclerosis
title_fullStr	Cuprizone and EAE mouse frontal cortex proteomics revealed proteins altered in multiple sclerosis
title_full_unstemmed	Cuprizone and EAE mouse frontal cortex proteomics revealed proteins altered in multiple sclerosis
title_sort	cuprizone and eae mouse frontal cortex proteomics revealed proteins altered in multiple sclerosis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/84b83fd96e1d4449be897044b5da5617
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Cuprizone and EAE mouse frontal cortex proteomics revealed proteins altered in multiple sclerosis

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