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Allopregnanolone and neuroinflammation: a focus on multiple sclerosis

The progesterone derivative allopregnanolone (ALLO) is one of the most widely studied compounds among neurosteroids. Through interactions with GABA-A receptors expressed by neurons and glial cells, ALLO has been shown to affect diverse aspects of neural cell physiology, including cell proliferation...

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Autores principales: Noorbakhsh, Farshid, Baker, Glen B., Power, Christopher
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4042158/
https://www.ncbi.nlm.nih.gov/pubmed/24917787
http://dx.doi.org/10.3389/fncel.2014.00134
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author Noorbakhsh, Farshid
Baker, Glen B.
Power, Christopher
author_facet Noorbakhsh, Farshid
Baker, Glen B.
Power, Christopher
author_sort Noorbakhsh, Farshid
collection PubMed
description The progesterone derivative allopregnanolone (ALLO) is one of the most widely studied compounds among neurosteroids. Through interactions with GABA-A receptors expressed by neurons and glial cells, ALLO has been shown to affect diverse aspects of neural cell physiology, including cell proliferation and survival, migration, and gene expression. Recent data point to important roles for ALLO in different neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, and multiple sclerosis (MS). Dysregulation in ALLO biosynthesis pathways has been reported in brain tissue from MS patients as well as in the central nervous system (CNS) tissue derived from MS animal models. Administration of ALLO has been shown to ameliorate neurobehavioral deficits together with neuropathology and inflammation in the CNS of animals with autoimmune demyelination. These findings are in line with previous reports indicating growth- and differentiation-promoting actions of ALLO on neurons and glial cells as well as its neuroprotective effects in the context of other CNS diseases. Nonetheless, these findings have also raised the possibility that ALLO might influence leukocyte biology and associated neuroinflammatory mechanisms independent of its neuroregenerative properties. Herein, we review the current knowledge regarding the role of ALLO in the pathogenesis of MS, and discuss the potential cellular and molecular pathways that might be influenced by ALLO in the context of disease.
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spelling pubmed-40421582014-06-10 Allopregnanolone and neuroinflammation: a focus on multiple sclerosis Noorbakhsh, Farshid Baker, Glen B. Power, Christopher Front Cell Neurosci Neuroscience The progesterone derivative allopregnanolone (ALLO) is one of the most widely studied compounds among neurosteroids. Through interactions with GABA-A receptors expressed by neurons and glial cells, ALLO has been shown to affect diverse aspects of neural cell physiology, including cell proliferation and survival, migration, and gene expression. Recent data point to important roles for ALLO in different neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, and multiple sclerosis (MS). Dysregulation in ALLO biosynthesis pathways has been reported in brain tissue from MS patients as well as in the central nervous system (CNS) tissue derived from MS animal models. Administration of ALLO has been shown to ameliorate neurobehavioral deficits together with neuropathology and inflammation in the CNS of animals with autoimmune demyelination. These findings are in line with previous reports indicating growth- and differentiation-promoting actions of ALLO on neurons and glial cells as well as its neuroprotective effects in the context of other CNS diseases. Nonetheless, these findings have also raised the possibility that ALLO might influence leukocyte biology and associated neuroinflammatory mechanisms independent of its neuroregenerative properties. Herein, we review the current knowledge regarding the role of ALLO in the pathogenesis of MS, and discuss the potential cellular and molecular pathways that might be influenced by ALLO in the context of disease. Frontiers Media S.A. 2014-06-03 /pmc/articles/PMC4042158/ /pubmed/24917787 http://dx.doi.org/10.3389/fncel.2014.00134 Text en Copyright © 2014 Noorbakhsh, Baker and Power. http://creativecommons.org/licenses/by/3.0/ 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) or licensor 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 Neuroscience
Noorbakhsh, Farshid
Baker, Glen B.
Power, Christopher
Allopregnanolone and neuroinflammation: a focus on multiple sclerosis
title Allopregnanolone and neuroinflammation: a focus on multiple sclerosis
title_full Allopregnanolone and neuroinflammation: a focus on multiple sclerosis
title_fullStr Allopregnanolone and neuroinflammation: a focus on multiple sclerosis
title_full_unstemmed Allopregnanolone and neuroinflammation: a focus on multiple sclerosis
title_short Allopregnanolone and neuroinflammation: a focus on multiple sclerosis
title_sort allopregnanolone and neuroinflammation: a focus on multiple sclerosis
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4042158/
https://www.ncbi.nlm.nih.gov/pubmed/24917787
http://dx.doi.org/10.3389/fncel.2014.00134
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