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Looking downstream: the role of cyclic AMP-regulated genes in axonal regeneration
Elevation of intracellular cyclic AMP (cAMP) levels has proven to be one of the most effective means of overcoming inhibition of axonal regeneration by myelin-associated inhibitors such as myelin-associated glycoprotein (MAG), Nogo, and oligodendrocyte myelin glycoprotein. Pharmacological manipulati...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2015
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4471816/ https://www.ncbi.nlm.nih.gov/pubmed/26150769 http://dx.doi.org/10.3389/fnmol.2015.00026 |
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author | Siddiq, Mustafa M. Hannila, Sari S. |
author_facet | Siddiq, Mustafa M. Hannila, Sari S. |
author_sort | Siddiq, Mustafa M. |
collection | PubMed |
description | Elevation of intracellular cyclic AMP (cAMP) levels has proven to be one of the most effective means of overcoming inhibition of axonal regeneration by myelin-associated inhibitors such as myelin-associated glycoprotein (MAG), Nogo, and oligodendrocyte myelin glycoprotein. Pharmacological manipulation of cAMP through the administration of dibutyryl cAMP or rolipram leads to enhanced axonal growth both in vivo and in vitro, and importantly, upregulation of cAMP within dorsal root ganglion neurons is responsible for the conditioning lesion effect, which indicates that cAMP plays a significant role in the endogenous mechanisms that promote axonal regeneration. The effects of cAMP are transcription-dependent and are mediated through the activation of protein kinase A (PKA) and the transcription factor cyclic AMP response element binding protein (CREB). This leads to the induction of a variety of genes, several of which have been shown to overcome myelin-mediated inhibition in their own right. In this review, we will highlight the pro-regenerative effects of arginase I (ArgI), interleukin (IL)-6, secretory leukocyte protease inhibitor (SLPI), and metallothionein (MT)-I/II, and discuss their potential for therapeutic use in spinal cord injury. |
format | Online Article Text |
id | pubmed-4471816 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-44718162015-07-06 Looking downstream: the role of cyclic AMP-regulated genes in axonal regeneration Siddiq, Mustafa M. Hannila, Sari S. Front Mol Neurosci Neuroscience Elevation of intracellular cyclic AMP (cAMP) levels has proven to be one of the most effective means of overcoming inhibition of axonal regeneration by myelin-associated inhibitors such as myelin-associated glycoprotein (MAG), Nogo, and oligodendrocyte myelin glycoprotein. Pharmacological manipulation of cAMP through the administration of dibutyryl cAMP or rolipram leads to enhanced axonal growth both in vivo and in vitro, and importantly, upregulation of cAMP within dorsal root ganglion neurons is responsible for the conditioning lesion effect, which indicates that cAMP plays a significant role in the endogenous mechanisms that promote axonal regeneration. The effects of cAMP are transcription-dependent and are mediated through the activation of protein kinase A (PKA) and the transcription factor cyclic AMP response element binding protein (CREB). This leads to the induction of a variety of genes, several of which have been shown to overcome myelin-mediated inhibition in their own right. In this review, we will highlight the pro-regenerative effects of arginase I (ArgI), interleukin (IL)-6, secretory leukocyte protease inhibitor (SLPI), and metallothionein (MT)-I/II, and discuss their potential for therapeutic use in spinal cord injury. Frontiers Media S.A. 2015-06-18 /pmc/articles/PMC4471816/ /pubmed/26150769 http://dx.doi.org/10.3389/fnmol.2015.00026 Text en Copyright © 2015 Siddiq and Hannila. http://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 and 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 Siddiq, Mustafa M. Hannila, Sari S. Looking downstream: the role of cyclic AMP-regulated genes in axonal regeneration |
title | Looking downstream: the role of cyclic AMP-regulated genes in axonal regeneration |
title_full | Looking downstream: the role of cyclic AMP-regulated genes in axonal regeneration |
title_fullStr | Looking downstream: the role of cyclic AMP-regulated genes in axonal regeneration |
title_full_unstemmed | Looking downstream: the role of cyclic AMP-regulated genes in axonal regeneration |
title_short | Looking downstream: the role of cyclic AMP-regulated genes in axonal regeneration |
title_sort | looking downstream: the role of cyclic amp-regulated genes in axonal regeneration |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4471816/ https://www.ncbi.nlm.nih.gov/pubmed/26150769 http://dx.doi.org/10.3389/fnmol.2015.00026 |
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