2. Academic Validation
  3. NOX4-derived ROS are neuroprotective by balancing intracellular calcium stores

NOX4-derived ROS are neuroprotective by balancing intracellular calcium stores

  • Cell Mol Life Sci. 2023 Apr 21;80(5):127. doi: 10.1007/s00018-023-04758-z.
Lukas Gola 1,  Laura Bierhansl 1,  Júlia Csatári 1,  Christina B Schroeter 2,  Lisanne Korn 1,  Venu Narayanan 1,  Manuela Cerina 1,  Sara Abdolahi 3,  Anna Speicher 1,  Alexander M Hermann 2,  Simone König 4,  Albena T Dinkova-Kostova 5,  Tawfeeq Shekh-Ahmad 6,  Sven G Meuth 2,  Heinz Wiendl 1,  Ali Gorji 3 7,  Matthias Pawlowski 1,  Stjepana Kovac 8
Affiliations

Affiliations

  • 1 Department of Neurology with Institute of Translational Neurology, University Hospital Münster, 48149, Münster, Germany.
  • 2 Department of Neurology, Medical Faculty, Heinrich Heine University Düsseldorf, 40225, Düsseldorf, Germany.
  • 3 Shefa Neuroscience Research Center, Khatam Alanbia Hospital, Tehran, Iran.
  • 4 Core Unit Proteomics, Interdisciplinary Center for Clinical Research, Medical Faculty, University of Münster, 48149, Münster, Germany.
  • 5 Division of Cellular Medicine, School of Medicine, University of Dundee, Dundee, DD1 9SY, UK.
  • 6 Institute for Drug Research, The School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, 91120, Jerusalem, Israel.
  • 7 Epilepsy Research Center, Westfälische Wilhelms-Universität Münster, 48149, Münster, Germany.
  • 8 Department of Neurology with Institute of Translational Neurology, University Hospital Münster, 48149, Münster, Germany. Stjepana.Kovac@ukmuenster.de.
PMID: 37081190 DOI: 10.1007/s00018-023-04758-z
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.

Keywords

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

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