NOX4-derived ROS are neuroprotective by balancing intracellular calcium stores

Lukas Gola, Laura Bierhansl, Júlia Csatári, Christina B. Schroeter, Lisanne Korn, Venu Narayanan, Manuela Cerina, Sara Abdolahi, Anna Speicher, Alexander M. Hermann, Simone König, Albena T. Dinkova-Kostova, Tawfeeq Shekh-Ahmad, Sven G. Meuth, Heinz Wiendl, Ali Gorji, Matthias Pawlowski, Stjepana Kovac*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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.

Original languageAmerican English
Article number127
JournalCellular and Molecular Life Sciences
Volume80
Issue number5
DOIs
StatePublished - 21 Apr 2023

Bibliographical note

Publisher Copyright:
© 2023, The Author(s).

Keywords

  • Calcium signaling
  • Hyperexcitability
  • Mitochondria
  • NADPH oxidase-4 (NOX4)
  • Neurodegeneration
  • Reactive oxygen species (ROS)

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