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mTOR and MAPK: from localized translation control to epilepsy
BACKGROUND: Epilepsy is one of the most common neurological diseases characterized by excessive hyperexcitability of neurons. Molecular mechanisms of epilepsy are diverse and not really understood. All in common is the misregulation of proteins that determine excitability such as potassium and sodiu...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5114760/ https://www.ncbi.nlm.nih.gov/pubmed/27855659 http://dx.doi.org/10.1186/s12868-016-0308-1 |
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author | Pernice, Helena F. Schieweck, Rico Kiebler, Michael A. Popper, Bastian |
author_facet | Pernice, Helena F. Schieweck, Rico Kiebler, Michael A. Popper, Bastian |
author_sort | Pernice, Helena F. |
collection | PubMed |
description | BACKGROUND: Epilepsy is one of the most common neurological diseases characterized by excessive hyperexcitability of neurons. Molecular mechanisms of epilepsy are diverse and not really understood. All in common is the misregulation of proteins that determine excitability such as potassium and sodium channels as well as GABA receptors; which are all known as biomarkers for epilepsy. Two recently identified key pathways involve the kinases mechanistic target of rapamycin (mTOR) and mitogen-activated protein kinases (MAPK). Interestingly, mRNAs coding for those biomarkers are found to be localized at or near synapses indicating a local misregulation of synthesis and activity. RESULTS: Research in the last decade indicates that RNA-binding proteins (RBPs) responsible for mRNA localization, stability and translation mediate local expression control. Among others, they are affected by mTOR and MAPK to guide expression of epileptic factors. These results suggest that mTOR/MAPK act on RBPs to regulate the fate of mRNAs, indicating a misregulation of protein expression at synapses in epilepsy. CONCLUSION: We propose that mTOR and MAPK regulate RBPs, thereby guiding the local expression of their target-mRNAs encoding for markers of epilepsy. Thus, misregulated mTOR/MAPK-RBP interplay may result in excessive local synthesis of ion channels and receptors thereby leading to hyperexcitability. Continuous stimulation of synapses further activates mTOR/MAPK pathway reinforcing their effect on RBP-mediated expression control establishing the basis for epilepsy. Here, we highlight findings showing the tight interplay between mTOR as well as MAPK with RBPs to control expression for epileptic biomarkers. |
format | Online Article Text |
id | pubmed-5114760 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-51147602016-11-25 mTOR and MAPK: from localized translation control to epilepsy Pernice, Helena F. Schieweck, Rico Kiebler, Michael A. Popper, Bastian BMC Neurosci Review BACKGROUND: Epilepsy is one of the most common neurological diseases characterized by excessive hyperexcitability of neurons. Molecular mechanisms of epilepsy are diverse and not really understood. All in common is the misregulation of proteins that determine excitability such as potassium and sodium channels as well as GABA receptors; which are all known as biomarkers for epilepsy. Two recently identified key pathways involve the kinases mechanistic target of rapamycin (mTOR) and mitogen-activated protein kinases (MAPK). Interestingly, mRNAs coding for those biomarkers are found to be localized at or near synapses indicating a local misregulation of synthesis and activity. RESULTS: Research in the last decade indicates that RNA-binding proteins (RBPs) responsible for mRNA localization, stability and translation mediate local expression control. Among others, they are affected by mTOR and MAPK to guide expression of epileptic factors. These results suggest that mTOR/MAPK act on RBPs to regulate the fate of mRNAs, indicating a misregulation of protein expression at synapses in epilepsy. CONCLUSION: We propose that mTOR and MAPK regulate RBPs, thereby guiding the local expression of their target-mRNAs encoding for markers of epilepsy. Thus, misregulated mTOR/MAPK-RBP interplay may result in excessive local synthesis of ion channels and receptors thereby leading to hyperexcitability. Continuous stimulation of synapses further activates mTOR/MAPK pathway reinforcing their effect on RBP-mediated expression control establishing the basis for epilepsy. Here, we highlight findings showing the tight interplay between mTOR as well as MAPK with RBPs to control expression for epileptic biomarkers. BioMed Central 2016-11-17 /pmc/articles/PMC5114760/ /pubmed/27855659 http://dx.doi.org/10.1186/s12868-016-0308-1 Text en © The Author(s) 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Review Pernice, Helena F. Schieweck, Rico Kiebler, Michael A. Popper, Bastian mTOR and MAPK: from localized translation control to epilepsy |
title | mTOR and MAPK: from localized translation control to epilepsy |
title_full | mTOR and MAPK: from localized translation control to epilepsy |
title_fullStr | mTOR and MAPK: from localized translation control to epilepsy |
title_full_unstemmed | mTOR and MAPK: from localized translation control to epilepsy |
title_short | mTOR and MAPK: from localized translation control to epilepsy |
title_sort | mtor and mapk: from localized translation control to epilepsy |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5114760/ https://www.ncbi.nlm.nih.gov/pubmed/27855659 http://dx.doi.org/10.1186/s12868-016-0308-1 |
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