TY - JOUR
T1 - NOX4-derived ROS are neuroprotective by balancing intracellular calcium stores
AU - Gola, Lukas
AU - Bierhansl, Laura
AU - Csatári, Júlia
AU - Schroeter, Christina B.
AU - Korn, Lisanne
AU - Narayanan, Venu
AU - Cerina, Manuela
AU - Abdolahi, Sara
AU - Speicher, Anna
AU - Hermann, Alexander M.
AU - König, Simone
AU - Dinkova-Kostova, Albena T.
AU - Shekh-Ahmad, Tawfeeq
AU - Meuth, Sven G.
AU - Wiendl, Heinz
AU - Gorji, Ali
AU - Pawlowski, Matthias
AU - Kovac, Stjepana
N1 - Publisher Copyright:
© 2023, The Author(s).
PY - 2023/4/21
Y1 - 2023/4/21
N2 - 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.
AB - 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.
KW - Calcium signaling
KW - Hyperexcitability
KW - Mitochondria
KW - NADPH oxidase-4 (NOX4)
KW - Neurodegeneration
KW - Reactive oxygen species (ROS)
UR - http://www.scopus.com/inward/record.url?scp=85153444985&partnerID=8YFLogxK
U2 - 10.1007/s00018-023-04758-z
DO - 10.1007/s00018-023-04758-z
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C2 - 37081190
AN - SCOPUS:85153444985
SN - 1420-682X
VL - 80
JO - Cellular and Molecular Life Sciences
JF - Cellular and Molecular Life Sciences
IS - 5
M1 - 127
ER -