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NOX4-derived ROS are neuroprotective by balancing intracellular calcium stores

Hyperexcitability is associated with neuronal dysfunction, cellular death, and consequently neurodegeneration. Redox disbalance can contribute to hyperexcitation and increased reactive oxygen species (ROS) levels are observed in various neurological diseases. NOX4 is an NADPH oxidase known to produc...

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Autores principales: Gola, Lukas, Bierhansl, Laura, Csatári, Júlia, Schroeter, Christina B., Korn, Lisanne, Narayanan, Venu, Cerina, Manuela, Abdolahi, Sara, Speicher, Anna, Hermann, Alexander M., König, Simone, Dinkova-Kostova, Albena T., Shekh-Ahmad, Tawfeeq, Meuth, Sven G., Wiendl, Heinz, Gorji, Ali, Pawlowski, Matthias, Kovac, Stjepana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10119225/
https://www.ncbi.nlm.nih.gov/pubmed/37081190
http://dx.doi.org/10.1007/s00018-023-04758-z
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author Gola, Lukas
Bierhansl, Laura
Csatári, Júlia
Schroeter, Christina B.
Korn, Lisanne
Narayanan, Venu
Cerina, Manuela
Abdolahi, Sara
Speicher, Anna
Hermann, Alexander M.
König, Simone
Dinkova-Kostova, Albena T.
Shekh-Ahmad, Tawfeeq
Meuth, Sven G.
Wiendl, Heinz
Gorji, Ali
Pawlowski, Matthias
Kovac, Stjepana
author_facet Gola, Lukas
Bierhansl, Laura
Csatári, Júlia
Schroeter, Christina B.
Korn, Lisanne
Narayanan, Venu
Cerina, Manuela
Abdolahi, Sara
Speicher, Anna
Hermann, Alexander M.
König, Simone
Dinkova-Kostova, Albena T.
Shekh-Ahmad, Tawfeeq
Meuth, Sven G.
Wiendl, Heinz
Gorji, Ali
Pawlowski, Matthias
Kovac, Stjepana
author_sort Gola, Lukas
collection PubMed
description Hyperexcitability is associated with neuronal dysfunction, cellular death, and consequently neurodegeneration. Redox disbalance can contribute to hyperexcitation and increased reactive oxygen species (ROS) levels are observed in various neurological diseases. NOX4 is an NADPH oxidase known to produce ROS and might have a regulating function during oxidative stress. We, therefore, aimed to determine the role of NOX4 on neuronal firing, hyperexcitability, and hyperexcitability-induced changes in neural network function. Using a multidimensional approach of an in vivo model of hyperexcitability, proteomic analysis, and cellular function analysis of ROS, mitochondrial integrity, and calcium levels, we demonstrate that NOX4 is neuroprotective by regulating ROS and calcium homeostasis and thereby preventing hyperexcitability and consequently neuronal death. These results implicate NOX4 as a potential redox regulator that is beneficial in hyperexcitability and thereby might have an important role in neurodegeneration. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00018-023-04758-z.
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spelling pubmed-101192252023-04-22 NOX4-derived ROS are neuroprotective by balancing intracellular calcium stores Gola, Lukas Bierhansl, Laura Csatári, Júlia Schroeter, Christina B. Korn, Lisanne Narayanan, Venu Cerina, Manuela Abdolahi, Sara Speicher, Anna Hermann, Alexander M. König, Simone Dinkova-Kostova, Albena T. Shekh-Ahmad, Tawfeeq Meuth, Sven G. Wiendl, Heinz Gorji, Ali Pawlowski, Matthias Kovac, Stjepana Cell Mol Life Sci Original Article Hyperexcitability is associated with neuronal dysfunction, cellular death, and consequently neurodegeneration. Redox disbalance can contribute to hyperexcitation and increased reactive oxygen species (ROS) levels are observed in various neurological diseases. NOX4 is an NADPH oxidase known to produce ROS and might have a regulating function during oxidative stress. We, therefore, aimed to determine the role of NOX4 on neuronal firing, hyperexcitability, and hyperexcitability-induced changes in neural network function. Using a multidimensional approach of an in vivo model of hyperexcitability, proteomic analysis, and cellular function analysis of ROS, mitochondrial integrity, and calcium levels, we demonstrate that NOX4 is neuroprotective by regulating ROS and calcium homeostasis and thereby preventing hyperexcitability and consequently neuronal death. These results implicate NOX4 as a potential redox regulator that is beneficial in hyperexcitability and thereby might have an important role in neurodegeneration. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00018-023-04758-z. Springer International Publishing 2023-04-21 2023 /pmc/articles/PMC10119225/ /pubmed/37081190 http://dx.doi.org/10.1007/s00018-023-04758-z Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Original Article
Gola, Lukas
Bierhansl, Laura
Csatári, Júlia
Schroeter, Christina B.
Korn, Lisanne
Narayanan, Venu
Cerina, Manuela
Abdolahi, Sara
Speicher, Anna
Hermann, Alexander M.
König, Simone
Dinkova-Kostova, Albena T.
Shekh-Ahmad, Tawfeeq
Meuth, Sven G.
Wiendl, Heinz
Gorji, Ali
Pawlowski, Matthias
Kovac, Stjepana
NOX4-derived ROS are neuroprotective by balancing intracellular calcium stores
title NOX4-derived ROS are neuroprotective by balancing intracellular calcium stores
title_full NOX4-derived ROS are neuroprotective by balancing intracellular calcium stores
title_fullStr NOX4-derived ROS are neuroprotective by balancing intracellular calcium stores
title_full_unstemmed NOX4-derived ROS are neuroprotective by balancing intracellular calcium stores
title_short NOX4-derived ROS are neuroprotective by balancing intracellular calcium stores
title_sort nox4-derived ros are neuroprotective by balancing intracellular calcium stores
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10119225/
https://www.ncbi.nlm.nih.gov/pubmed/37081190
http://dx.doi.org/10.1007/s00018-023-04758-z
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