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Mechanism of Siponimod: Anti-Inflammatory and Neuroprotective Mode of Action
Multiple sclerosis (MS) is a neuroinflammatory disorder of the central nervous system (CNS), and represents one of the main causes of disability in young adults. On the histopathological level, the disease is characterized by inflammatory demyelination and diffuse neurodegeneration. Although on the...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356776/ https://www.ncbi.nlm.nih.gov/pubmed/30621015 http://dx.doi.org/10.3390/cells8010024 |
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author | Behrangi, Newshan Fischbach, Felix Kipp, Markus |
author_facet | Behrangi, Newshan Fischbach, Felix Kipp, Markus |
author_sort | Behrangi, Newshan |
collection | PubMed |
description | Multiple sclerosis (MS) is a neuroinflammatory disorder of the central nervous system (CNS), and represents one of the main causes of disability in young adults. On the histopathological level, the disease is characterized by inflammatory demyelination and diffuse neurodegeneration. Although on the surface the development of new inflammatory CNS lesions in MS may appear consistent with a primary recruitment of peripheral immune cells, questions have been raised as to whether lymphocyte and/or monocyte invasion into the brain are really at the root of inflammatory lesion development. In this review article, we discuss a less appreciated inflammation-neurodegeneration interplay, that is: Neurodegeneration can trigger the formation of new, focal inflammatory lesions. We summarize old and recent findings suggesting that new inflammatory lesions develop at sites of focal or diffuse degenerative processes within the CNS. Such a concept is discussed in the context of the EXPAND trial, showing that siponimod exerts anti-inflammatory and neuroprotective activities in secondary progressive MS patients. The verification or rejection of such a concept is vital for the development of new therapeutic strategies for progressive MS. |
format | Online Article Text |
id | pubmed-6356776 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-63567762019-02-06 Mechanism of Siponimod: Anti-Inflammatory and Neuroprotective Mode of Action Behrangi, Newshan Fischbach, Felix Kipp, Markus Cells Review Multiple sclerosis (MS) is a neuroinflammatory disorder of the central nervous system (CNS), and represents one of the main causes of disability in young adults. On the histopathological level, the disease is characterized by inflammatory demyelination and diffuse neurodegeneration. Although on the surface the development of new inflammatory CNS lesions in MS may appear consistent with a primary recruitment of peripheral immune cells, questions have been raised as to whether lymphocyte and/or monocyte invasion into the brain are really at the root of inflammatory lesion development. In this review article, we discuss a less appreciated inflammation-neurodegeneration interplay, that is: Neurodegeneration can trigger the formation of new, focal inflammatory lesions. We summarize old and recent findings suggesting that new inflammatory lesions develop at sites of focal or diffuse degenerative processes within the CNS. Such a concept is discussed in the context of the EXPAND trial, showing that siponimod exerts anti-inflammatory and neuroprotective activities in secondary progressive MS patients. The verification or rejection of such a concept is vital for the development of new therapeutic strategies for progressive MS. MDPI 2019-01-07 /pmc/articles/PMC6356776/ /pubmed/30621015 http://dx.doi.org/10.3390/cells8010024 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Behrangi, Newshan Fischbach, Felix Kipp, Markus Mechanism of Siponimod: Anti-Inflammatory and Neuroprotective Mode of Action |
title | Mechanism of Siponimod: Anti-Inflammatory and Neuroprotective Mode of Action |
title_full | Mechanism of Siponimod: Anti-Inflammatory and Neuroprotective Mode of Action |
title_fullStr | Mechanism of Siponimod: Anti-Inflammatory and Neuroprotective Mode of Action |
title_full_unstemmed | Mechanism of Siponimod: Anti-Inflammatory and Neuroprotective Mode of Action |
title_short | Mechanism of Siponimod: Anti-Inflammatory and Neuroprotective Mode of Action |
title_sort | mechanism of siponimod: anti-inflammatory and neuroprotective mode of action |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356776/ https://www.ncbi.nlm.nih.gov/pubmed/30621015 http://dx.doi.org/10.3390/cells8010024 |
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