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Thyroid hormone-dependent oligodendroglial cell lineage genomic and non-genomic signaling through integrin receptors
Multiple sclerosis (MS) is a heterogeneous autoimmune disease whereby the pathological sequelae evolve from oligodendrocytes (OLs) within the central nervous system and are targeted by the immune system, which causes widespread white matter pathology and results in neuronal dysfunction and neurologi...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9483185/ https://www.ncbi.nlm.nih.gov/pubmed/36133808 http://dx.doi.org/10.3389/fphar.2022.934971 |
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author | Emamnejad, Rahimeh Dass, Mary Mahlis, Michael Bozkurt, Salome Ye, Sining Pagnin, Maurice Theotokis, Paschalis Grigoriadis, Nikolaos Petratos, Steven |
author_facet | Emamnejad, Rahimeh Dass, Mary Mahlis, Michael Bozkurt, Salome Ye, Sining Pagnin, Maurice Theotokis, Paschalis Grigoriadis, Nikolaos Petratos, Steven |
author_sort | Emamnejad, Rahimeh |
collection | PubMed |
description | Multiple sclerosis (MS) is a heterogeneous autoimmune disease whereby the pathological sequelae evolve from oligodendrocytes (OLs) within the central nervous system and are targeted by the immune system, which causes widespread white matter pathology and results in neuronal dysfunction and neurological impairment. The progression of this disease is facilitated by a failure in remyelination following chronic demyelination. One mediator of remyelination is thyroid hormone (TH), whose reliance on monocarboxylate transporter 8 (MCT8) was recently defined. MCT8 facilitates the entry of THs into oligodendrocyte progenitor cell (OPC) and pre-myelinating oligodendrocytes (pre-OLs). Patients with MS may exhibit downregulated MCT8 near inflammatory lesions, which emphasizes an inhibition of TH signaling and subsequent downstream targeted pathways such as phosphoinositide 3-kinase (PI3K)-Akt. However, the role of the closely related mammalian target of rapamycin (mTOR) in pre-OLs during neuroinflammation may also be central to the remyelination process and is governed by various growth promoting signals. Recent research indicates that this may be reliant on TH-dependent signaling through β1-integrins. This review identifies genomic and non-genomic signaling that is regulated through mTOR in TH-responsive pre-OLs and mature OLs in mouse models of MS. This review critiques data that implicates non-genomic Akt and mTOR signaling in response to TH-dependent integrin receptor activation in pre-OLs. We have also examined whether this can drive remyelination in the context of neuroinflammation and associated sequelae. Importantly, we outline how novel therapeutic small molecules are being designed to target integrin receptors on oligodendroglial lineage cells and whether these are viable therapeutic options for future use in clinical trials for MS. |
format | Online Article Text |
id | pubmed-9483185 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-94831852022-09-20 Thyroid hormone-dependent oligodendroglial cell lineage genomic and non-genomic signaling through integrin receptors Emamnejad, Rahimeh Dass, Mary Mahlis, Michael Bozkurt, Salome Ye, Sining Pagnin, Maurice Theotokis, Paschalis Grigoriadis, Nikolaos Petratos, Steven Front Pharmacol Pharmacology Multiple sclerosis (MS) is a heterogeneous autoimmune disease whereby the pathological sequelae evolve from oligodendrocytes (OLs) within the central nervous system and are targeted by the immune system, which causes widespread white matter pathology and results in neuronal dysfunction and neurological impairment. The progression of this disease is facilitated by a failure in remyelination following chronic demyelination. One mediator of remyelination is thyroid hormone (TH), whose reliance on monocarboxylate transporter 8 (MCT8) was recently defined. MCT8 facilitates the entry of THs into oligodendrocyte progenitor cell (OPC) and pre-myelinating oligodendrocytes (pre-OLs). Patients with MS may exhibit downregulated MCT8 near inflammatory lesions, which emphasizes an inhibition of TH signaling and subsequent downstream targeted pathways such as phosphoinositide 3-kinase (PI3K)-Akt. However, the role of the closely related mammalian target of rapamycin (mTOR) in pre-OLs during neuroinflammation may also be central to the remyelination process and is governed by various growth promoting signals. Recent research indicates that this may be reliant on TH-dependent signaling through β1-integrins. This review identifies genomic and non-genomic signaling that is regulated through mTOR in TH-responsive pre-OLs and mature OLs in mouse models of MS. This review critiques data that implicates non-genomic Akt and mTOR signaling in response to TH-dependent integrin receptor activation in pre-OLs. We have also examined whether this can drive remyelination in the context of neuroinflammation and associated sequelae. Importantly, we outline how novel therapeutic small molecules are being designed to target integrin receptors on oligodendroglial lineage cells and whether these are viable therapeutic options for future use in clinical trials for MS. Frontiers Media S.A. 2022-09-05 /pmc/articles/PMC9483185/ /pubmed/36133808 http://dx.doi.org/10.3389/fphar.2022.934971 Text en Copyright © 2022 Emamnejad, Dass, Mahlis, Bozkurt, Ye, Pagnin, Theotokis, Grigoriadis and Petratos. 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 | Pharmacology Emamnejad, Rahimeh Dass, Mary Mahlis, Michael Bozkurt, Salome Ye, Sining Pagnin, Maurice Theotokis, Paschalis Grigoriadis, Nikolaos Petratos, Steven Thyroid hormone-dependent oligodendroglial cell lineage genomic and non-genomic signaling through integrin receptors |
title | Thyroid hormone-dependent oligodendroglial cell lineage genomic and non-genomic signaling through integrin receptors |
title_full | Thyroid hormone-dependent oligodendroglial cell lineage genomic and non-genomic signaling through integrin receptors |
title_fullStr | Thyroid hormone-dependent oligodendroglial cell lineage genomic and non-genomic signaling through integrin receptors |
title_full_unstemmed | Thyroid hormone-dependent oligodendroglial cell lineage genomic and non-genomic signaling through integrin receptors |
title_short | Thyroid hormone-dependent oligodendroglial cell lineage genomic and non-genomic signaling through integrin receptors |
title_sort | thyroid hormone-dependent oligodendroglial cell lineage genomic and non-genomic signaling through integrin receptors |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9483185/ https://www.ncbi.nlm.nih.gov/pubmed/36133808 http://dx.doi.org/10.3389/fphar.2022.934971 |
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