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Gap junctions and hemichannels composed of connexins: potential therapeutic targets for neurodegenerative diseases
Microglia are macrophage-like resident immune cells that contribute to the maintenance of homeostasis in the central nervous system (CNS). Abnormal activation of microglia can cause damage in the CNS, and accumulation of activated microglia is a characteristic pathological observation in neurologic...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2014
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4151093/ https://www.ncbi.nlm.nih.gov/pubmed/25228858 http://dx.doi.org/10.3389/fncel.2014.00189 |
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author | Takeuchi, Hideyuki Suzumura, Akio |
author_facet | Takeuchi, Hideyuki Suzumura, Akio |
author_sort | Takeuchi, Hideyuki |
collection | PubMed |
description | Microglia are macrophage-like resident immune cells that contribute to the maintenance of homeostasis in the central nervous system (CNS). Abnormal activation of microglia can cause damage in the CNS, and accumulation of activated microglia is a characteristic pathological observation in neurologic conditions such as trauma, stroke, inflammation, epilepsy, and neurodegenerative diseases. Activated microglia secrete high levels of glutamate, which damages CNS cells and has been implicated as a major cause of neurodegeneration in these conditions. Glutamate-receptor blockers and microglia inhibitors (e.g., minocycline) have been examined as therapeutic candidates for several neurodegenerative diseases; however, these compounds exerted little therapeutic benefit because they either perturbed physiological glutamate signals or suppressed the actions of protective microglia. The ideal therapeutic approach would hamper the deleterious roles of activated microglia without diminishing their protective effects. We recently found that abnormally activated microglia secrete glutamate via gap-junction hemichannels on the cell surface. Moreover, administration of gap-junction inhibitors significantly suppressed excessive microglial glutamate release and improved disease symptoms in animal models of neurologic conditions such as stroke, multiple sclerosis, amyotrophic lateral sclerosis, and Alzheimer's disease. Recent evidence also suggests that neuronal and glial communication via gap junctions amplifies neuroinflammation and neurodegeneration. Elucidation of the precise pathologic roles of gap junctions and hemichannels may lead to a novel therapeutic strategies that can slow and halt the progression of neurodegenerative diseases. |
format | Online Article Text |
id | pubmed-4151093 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-41510932014-09-16 Gap junctions and hemichannels composed of connexins: potential therapeutic targets for neurodegenerative diseases Takeuchi, Hideyuki Suzumura, Akio Front Cell Neurosci Neuroscience Microglia are macrophage-like resident immune cells that contribute to the maintenance of homeostasis in the central nervous system (CNS). Abnormal activation of microglia can cause damage in the CNS, and accumulation of activated microglia is a characteristic pathological observation in neurologic conditions such as trauma, stroke, inflammation, epilepsy, and neurodegenerative diseases. Activated microglia secrete high levels of glutamate, which damages CNS cells and has been implicated as a major cause of neurodegeneration in these conditions. Glutamate-receptor blockers and microglia inhibitors (e.g., minocycline) have been examined as therapeutic candidates for several neurodegenerative diseases; however, these compounds exerted little therapeutic benefit because they either perturbed physiological glutamate signals or suppressed the actions of protective microglia. The ideal therapeutic approach would hamper the deleterious roles of activated microglia without diminishing their protective effects. We recently found that abnormally activated microglia secrete glutamate via gap-junction hemichannels on the cell surface. Moreover, administration of gap-junction inhibitors significantly suppressed excessive microglial glutamate release and improved disease symptoms in animal models of neurologic conditions such as stroke, multiple sclerosis, amyotrophic lateral sclerosis, and Alzheimer's disease. Recent evidence also suggests that neuronal and glial communication via gap junctions amplifies neuroinflammation and neurodegeneration. Elucidation of the precise pathologic roles of gap junctions and hemichannels may lead to a novel therapeutic strategies that can slow and halt the progression of neurodegenerative diseases. Frontiers Media S.A. 2014-09-02 /pmc/articles/PMC4151093/ /pubmed/25228858 http://dx.doi.org/10.3389/fncel.2014.00189 Text en Copyright © 2014 Takeuchi and Suzumura. 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 Takeuchi, Hideyuki Suzumura, Akio Gap junctions and hemichannels composed of connexins: potential therapeutic targets for neurodegenerative diseases |
title | Gap junctions and hemichannels composed of connexins: potential therapeutic targets for neurodegenerative diseases |
title_full | Gap junctions and hemichannels composed of connexins: potential therapeutic targets for neurodegenerative diseases |
title_fullStr | Gap junctions and hemichannels composed of connexins: potential therapeutic targets for neurodegenerative diseases |
title_full_unstemmed | Gap junctions and hemichannels composed of connexins: potential therapeutic targets for neurodegenerative diseases |
title_short | Gap junctions and hemichannels composed of connexins: potential therapeutic targets for neurodegenerative diseases |
title_sort | gap junctions and hemichannels composed of connexins: potential therapeutic targets for neurodegenerative diseases |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4151093/ https://www.ncbi.nlm.nih.gov/pubmed/25228858 http://dx.doi.org/10.3389/fncel.2014.00189 |
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