{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T01:54:31Z","timestamp":1793066071975,"version":"4.5.0"},"reference-count":65,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T00:00:00Z","timestamp":1694649600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Spinal muscular atrophy (SMA) is a fatal neurodegenerative disorder, characterized by motor neuron (MN) degeneration and severe muscular atrophy and caused by Survival of Motor Neuron (SMN) depletion. Therapies aimed at increasing SMN in patients have proven their efficiency in alleviating SMA symptoms but not for all patients. Thus, combinational therapies are warranted. Here, we investigated the involvement of NADPH oxidase 4 (NOX4) in SMA-induced spinal MN death and if the modulation of Nox4 activity could be beneficial for SMA patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analysed in the spinal cord of severe type SMA-like mice before and at the disease onset, the level of oxidative stress and Nox4 expression. Then, we tested the effect of Nox4 inhibition by GKT137831\/Setanaxib, a drug presently in clinical development, by intrathecal injection on MN survival and motor behaviour. Finally, we tested if GKT137831\/Setanaxib could act synergistically with FDA-validated SMN-upregulating treatment (nusinersen).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We show that NOX4 is overexpressed in SMA and its inhibition by GKT137831\/Setanaxib protected spinal MN from SMA-induced degeneration. These improvements were associated with a significant increase in lifespan and motor behaviour of the mice. At the molecular level, GKT137831 activated the pro-survival AKT\/CREB signaling pathway, leading to an increase in SMN expression in SMA MNs. Most importantly, we found that the\n                      <jats:italic>per os<\/jats:italic>\n                      administration of GKT137831 acted synergistically with a FDA-validated SMN-upregulating treatment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The pharmacological inhibition of NOX4 by GKT137831\/Setanaxib is neuroprotector and could represent a complementary therapeutic strategy to fight against SMA.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fncel.2023.1242828","type":"journal-article","created":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T09:26:43Z","timestamp":1694683603000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["NADPH oxidase 4 inhibition is a complementary therapeutic strategy for spinal muscular atrophy"],"prefix":"10.3389","volume":"17","author":[{"given":"Mirella","family":"El Khoury","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Biondi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaelle","family":"Bruneteau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delphine","family":"Sapaly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Bendris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia","family":"Bezier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zo\u00e9","family":"Clerc","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elias Abi","family":"Akar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laure","family":"Weill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Assaad A.","family":"Eid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Charbonnier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,9,14]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1016\/j.jphs.2020.09.001","article-title":"Survival motor neuron protein regulates oxidative stress and inflammatory response in microglia of the spinal cord in spinal muscular atrophy","volume":"144","author":"Ando","year":"2020","journal-title":"J. Pharmacol. Sci."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"2316","DOI":"10.1002\/hep.25938","article-title":"Nicotinamide adenine dinucleotide phosphate oxidase in experimental liver fibrosis: GKT137831 as a novel potential therapeutic agent","volume":"56","author":"Aoyama","year":"2012","journal-title":"Hepatology"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1007\/s00401-003-0743-9","article-title":"Neuropathological analysis in spinal muscular atrophy type II","volume":"106","author":"Araki","year":"2003","journal-title":"Acta Neuropathol."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1089\/152308602753625834","article-title":"The activity of leukocyte NADPH oxidase: regulation by p47PHOX cysteine and serine residues","volume":"4","author":"Babior","year":"2002","journal-title":"Antioxid. Redox Signal."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1038\/nrd1330","article-title":"Neurodegenerative diseases and oxidative stress","volume":"3","author":"Barnham","year":"2004","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1152\/physrev.00044.2005","article-title":"The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology","volume":"87","author":"Bedard","year":"2007","journal-title":"Physiol. Rev."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"3029","DOI":"10.1074\/jbc.M116.752261","article-title":"NADPH oxidase 4 (Nox4) suppresses mitochondrial biogenesis and bioenergetics in lung fibroblasts via a nuclear factor erythroid-derived 2-like 2 (Nrf2)-dependent pathway","volume":"292","author":"Bernard","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"12063","DOI":"10.1523\/JNEUROSCI.0608-15.2015","article-title":"IGF-1R reduction triggers neuroprotective signaling pathways in spinal muscular atrophy mice","volume":"35","author":"Biondi","year":"2015","journal-title":"J. Neurosci."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"11288","DOI":"10.1523\/JNEUROSCI.1764-10.2010","article-title":"In Vivo NMDA receptor activation accelerates motor unit maturation, protects spinal motor neurons, and enhances SMN2 gene expression in severe spinal muscular atrophy mice","volume":"30","author":"Biondi","year":"2010","journal-title":"J. Neurosci."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"4280","DOI":"10.1523\/JNEUROSCI.2728-12.2013","article-title":"Shift from extracellular signal-regulated kinase to AKT\/cAMP response element-binding protein pathway increases survival-motor-neuron expression in spinal-muscular-atrophy-like mice and patient cells","volume":"33","author":"Branchu","year":"2013","journal-title":"J. Neurosci."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1016\/j.brainres.2015.08.031","article-title":"How microglia kill neurons","volume":"1628","author":"Brown","year":"2015","journal-title":"Brain Res."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"eaai8710","DOI":"10.1126\/scitranslmed.aai8710","article-title":"Targeting the vascular and perivascular niches as a regenerative therapy for lung and liver fibrosis","volume":"9","author":"Cao","year":"2017","journal-title":"Sci. Transl. Med."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"261","DOI":"10.3389\/fncel.2013.00261","article-title":"NMDA modulates oligodendrocyte differentiation of subventricular zone cells through PKC activation","volume":"7","author":"Cavaliere","year":"2013","journal-title":"Front. Cell. Neurosci."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"1229","DOI":"10.1089\/ars.2011.4489","article-title":"NADPH oxidases as regulators of tumor angiogenesis: current and emerging concepts","volume":"16","author":"Coso","year":"2012","journal-title":"Antioxid. Redox Signal."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"3017","DOI":"10.1016\/S0140-6736(16)31408-8","article-title":"Treatment of infantile-onset spinal muscular atrophy with nusinersen: a phase 2, open-label, dose-escalation study","volume":"388","author":"Finkel","year":"2016","journal-title":"Lancet"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"1723","DOI":"10.1056\/NEJMoa1702752","article-title":"Nusinersen versus sham control in infantile-onset spinal muscular atrophy","volume":"377","author":"Finkel","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"e921","DOI":"10.1371\/journal.pone.0000921","article-title":"Ribonucleoprotein assembly defects correlate with spinal muscular atrophy severity and preferentially affect a subset of Spliceosomal snRNPs","volume":"2","author":"Gabanella","year":"2007","journal-title":"PLoS One"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"1160","DOI":"10.2174\/15665240113139990044","article-title":"At the \u201cjunction\u201d of spinal muscular atrophy pathogenesis: the role of neuromuscular junction dysfunction in SMA disease progression","volume":"13","author":"Goulet","year":"2013","journal-title":"Curr. Mol. Med."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1016\/j.celrep.2013.09.017","article-title":"mTORC1 targets the translational repressor 4E-BP2, but not S6 kinase 1\/2, to regulate neural stem cell self-renewal in Vivo","volume":"5","author":"Hartman","year":"2013","journal-title":"Cell Rep."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"770","DOI":"10.1016\/s0387-7604(02)00103-1","article-title":"Oxidative stress and disturbed glutamate transport in spinal muscular atrophy","volume":"24","author":"Hayashi","year":"2002","journal-title":"Brain Dev."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"321","DOI":"10.2174\/157015912804499483","article-title":"NADPH oxidase and neurodegeneration","volume":"10","author":"Hernandes","year":"2012","journal-title":"Curr. Neuropharmacol."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"1359","DOI":"10.1038\/s41593-018-0242-x","article-title":"Microglia in neurodegeneration","volume":"21","author":"Hickman","year":"2018","journal-title":"Nat. Neurosci."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"1981","DOI":"10.1091\/mbc.e08-12-1248","article-title":"Nutrient-dependent mTORC1 association with the ULK1\u2013Atg13\u2013FIP200 complex required for autophagy","volume":"20","author":"Hosokawa","year":"2009","journal-title":"MBoC"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1038\/71709","article-title":"A mouse model for spinal muscular atrophy","volume":"24","author":"Hsieh-Li","year":"2000","journal-title":"Nat. Genet."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"e0191034","DOI":"10.1371\/journal.pone.0191034","article-title":"Oxidative stress caused by activation of NADPH oxidase 4 promotes contrast-induced acute kidney injury","volume":"13","author":"Jeong","year":"2018","journal-title":"PLoS One"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"4651","DOI":"10.1042\/BCJ20160845","article-title":"mTORC1 signalling and eIF4E\/4E-BP1 translation initiation factor stoichiometry influence recombinant protein productivity from GS-CHOK1 cells","volume":"473","author":"Joss\u00e9","year":"2016","journal-title":"Biochem. J."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.mito.2006.11.017","article-title":"Mitochondrial transcription factor a (TFAM): roles in maintenance of mtDNA and cellular functions","volume":"7","author":"Kang","year":"2007","journal-title":"Mitochondrion"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/j.nmd.2020.12.006","article-title":"Nusinersen treatment of older children and adults with spinal muscular atrophy","volume":"31","author":"Konersman","year":"2021","journal-title":"Neuromuscul. Disord."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"1374","DOI":"10.1006\/bbrc.1994.1603","article-title":"Low levels of mitochondrial transcription factor a in mitochondrial DNA depletion","volume":"200","author":"Larsson","year":"1994","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"1239","DOI":"10.1038\/s41556-020-00577-7","article-title":"SMN-primed ribosomes modulate the translation of transcripts related to spinal muscular atrophy","volume":"22","author":"Lauria","year":"2020","journal-title":"Nat. Cell Biol."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.stem.2010.11.028","article-title":"Proliferative neural stem cells have high endogenous ROS levels that regulate self-renewal and neurogenesis in a PI3K\/Akt-Dependant manner","volume":"8","author":"le Belle","year":"2011","journal-title":"Cell Stem Cell"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/0092-8674(95)90460-3","article-title":"Identification and characterization of a spinal muscular atrophy-determining gene","volume":"80","author":"Lefebvre","year":"1995","journal-title":"Cells"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1093\/hmg\/9.2.259","article-title":"An exonic enhancer is required for inclusion of an essential exon in the SMA-determining gene SMN","volume":"9","author":"Lorson","year":"2000","journal-title":"Hum. Mol. Genet."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"6307","DOI":"10.1073\/pnas.96.11.6307","article-title":"A single nucleotide in the SMN gene regulates splicing and is responsible for spinal muscular atrophy","volume":"96","author":"Lorson","year":"1999","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1016\/S0021-9258(19)52451-6","article-title":"Protein measurement with the Folin phenol reagent","volume":"193","author":"Lowry","year":"1951","journal-title":"J. Biol. Chem."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1016\/j.nurt.2010.05.014","article-title":"Microglial activation and chronic neurodegeneration","volume":"7","author":"Lull","year":"2010","journal-title":"Neurotherapeutics"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1161\/ATVBAHA.109.193896","article-title":"JAK\/STAT signaling pathway regulates Nox1 and Nox4-based NADPH oxidase in human aortic smooth muscle cells","volume":"30","author":"Manea","year":"2010","journal-title":"ATVB"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.cellsig.2005.03.023","article-title":"Functional analysis of Nox4 reveals unique characteristics compared to other NADPH oxidases","volume":"18","author":"Martyn","year":"2006","journal-title":"Cell. Signal."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"1713","DOI":"10.1056\/NEJMoa1706198","article-title":"Single-dose gene-replacement therapy for spinal muscular atrophy","volume":"377","author":"Mendell","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1056\/NEJMoa1710504","article-title":"Nusinersen versus sham control in later-onset spinal muscular atrophy","volume":"378","author":"Mercuri","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"688","DOI":"10.1126\/science.1250127","article-title":"Motor neuron disease. SMN2 splicing modifiers improve motor function and longevity in mice with spinal muscular atrophy","volume":"345","author":"Naryshkin","year":"2014","journal-title":"Science"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"2433","DOI":"10.1021\/bi9022285","article-title":"Constitutive NADPH-dependent Electron transferase activity of the Nox4 dehydrogenase domain","volume":"49","author":"Nisimoto","year":"2010","journal-title":"Biochemistry"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"3701","DOI":"10.1038\/s41598-019-39788-w","article-title":"Notch signaling mediates astrocyte abnormality in spinal muscular atrophy model systems","volume":"9","author":"Ohuchi","year":"2019","journal-title":"Sci. Rep."},{"key":"ref44","doi-asserted-by":"publisher","first-page":"514","DOI":"10.1093\/hmg\/ddv489","article-title":"SMN deficiency does not induce oxidative stress in SMA iPSC-derived astrocytes or motor neurons","volume":"25","author":"Patitucci","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"ref45","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1002\/ana.410440518","article-title":"Protein modification by the lipid peroxidation product 4-hydroxynonenal in the spinal cords of amyotrophic lateral sclerosis patients","volume":"44","author":"Pedersen","year":"1998","journal-title":"Ann. Neurol."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"3223","DOI":"10.1038\/s41419-017-0086-4","article-title":"Inhibition of autophagy delays motoneuron degeneration and extends lifespan in a mouse model of spinal muscular atrophy","volume":"8","author":"Piras","year":"2017","journal-title":"Cell Death Dis."},{"key":"ref47","doi-asserted-by":"publisher","first-page":"760","DOI":"10.1189\/jlb.0404216","article-title":"Structure and regulation of the neutrophil respiratory burst oxidase: comparison with nonphagocyte oxidases","volume":"76","author":"Quinn","year":"2004","journal-title":"J. Leukoc. Biol."},{"key":"ref48","doi-asserted-by":"publisher","first-page":"6501","DOI":"10.1021\/acs.jmedchem.8b00741","article-title":"Discovery of Risdiplam, a selective survival of motor Neuron-2 (SMN2) gene splicing modifier for the treatment of spinal muscular atrophy (SMA)","volume":"61","author":"Ratni","year":"2018","journal-title":"J. Med. Chem."},{"key":"ref49","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1124\/jpet.113.212407","article-title":"Pharmacology of a central nervous system delivered 2\u2032- O -Methoxyethyl\u2013modified survival of motor neuron splicing oligonucleotide in mice and nonhuman Primates","volume":"350","author":"Rigo","year":"2014","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref50","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1007\/978-1-61779-370-7_6","article-title":"AAV-mediated liver-directed gene therapy","volume":"807","author":"Sands","year":"2011","journal-title":"Methods Mol. Biol."},{"key":"ref51","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1186\/s40478-021-01223-5","article-title":"Spinal muscular atrophy autophagy profile is tissue-dependent: differential regulation between muscle and motoneurons","volume":"9","author":"Sansa","year":"2021","journal-title":"Acta Neuropathol. Commun."},{"key":"ref52","doi-asserted-by":"publisher","first-page":"2075","DOI":"10.1038\/s41598-018-20219-1","article-title":"Small-molecule flunarizine increases SMN protein in nuclear Cajal bodies and motor function in a mouse model of spinal muscular atrophy","volume":"8","author":"Sapaly","year":"2018","journal-title":"Sci. Rep."},{"key":"ref53","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1016\/S0197-4580(01)00327-X","article-title":"The effect of increased concentrations of homocysteine on the concentration of (E)-4-hydroxy-2-nonenal in the plasma and cerebrospinal fluid of patients with Alzheimer\u2019s disease","volume":"23","author":"Selley","year":"2002","journal-title":"Neurobiol. Aging"},{"key":"ref54","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1042\/BJ20061903","article-title":"NOX4 activity is determined by mRNA levels and reveals a unique pattern of ROS generation","volume":"406","author":"Serrander","year":"2007","journal-title":"Biochem. J."},{"key":"ref55","doi-asserted-by":"publisher","first-page":"1074","DOI":"10.1016\/j.yjmcc.2012.01.005","article-title":"Partial restoration of cardio-vascular defects in a rescued severe model of spinal muscular atrophy","volume":"52","author":"Shababi","year":"2012","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref56","doi-asserted-by":"publisher","first-page":"3781","DOI":"10.1038\/s41598-018-21838-4","article-title":"Nox4 is a target for Tuberin deficiency syndrome","volume":"8","author":"Shi","year":"2018","journal-title":"Sci. Rep."},{"key":"ref57","doi-asserted-by":"publisher","first-page":"341","DOI":"10.4161\/rna.6.3.8723","article-title":"A short antisense oligonucleotide masking a unique intronic motif prevents skipping of a critical exon in spinal muscular atrophy","volume":"6","author":"Singh","year":"2009","journal-title":"RNA Biol."},{"key":"ref58","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1186\/s40478-020-01101-6","article-title":"Mitochondrial defects in the respiratory complex I contribute to impaired translational initiation via ROS and energy homeostasis in SMA motor neurons","volume":"8","author":"Thelen","year":"2020","journal-title":"Acta Neuropathol. Commun."},{"key":"ref59","first-page":"A2427","article-title":"Post-transcriptional regulation of NOX4 by the Mechanosensing ROCK\/mTOR pathway","volume-title":"A74. Matrix: drivers and targets","author":"Venado","year":"2016"},{"key":"ref60","doi-asserted-by":"publisher","first-page":"CD006281","DOI":"10.1002\/14651858.CD006281.pub5","article-title":"Drug treatment for spinal muscular atrophy type I","volume":"12","author":"Wadman","year":"2019","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref61","doi-asserted-by":"publisher","first-page":"12132","DOI":"10.1073\/pnas.0603670103","article-title":"The inflammatory NADPH oxidase enzyme modulates motor neuron degeneration in amyotrophic lateral sclerosis mice","volume":"103","author":"Wu","year":"2006","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"ref62","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2019\/3585390","article-title":"NADPH oxidase 4 contributes to myoblast fusion and skeletal muscle regeneration","volume":"2019","author":"Youm","year":"2019","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref63","first-page":"7","article-title":"On genetic heterogeneity, anticipation, and imprinting in polycystic kidney diseases","volume":"10","author":"Zerres","year":"1995","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref64","doi-asserted-by":"publisher","first-page":"8622","DOI":"10.1523\/JNEUROSCI.3967-05.2006","article-title":"Multiprotein complexes of the survival of motor neuron protein SMN with Gemins traffic to neuronal processes and growth cones of motor neurons","volume":"26","author":"Zhang","year":"2006","journal-title":"J. Neurosci."},{"key":"ref65","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1161\/CIRCULATIONAHA.114.011079","article-title":"NADPH oxidase 4 induces cardiac fibrosis and hypertrophy through activating Akt\/mTOR and NF\u03baB signaling pathways","volume":"131","author":"Zhao","year":"2015","journal-title":"Circulation"}],"container-title":["Frontiers in Cellular Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fncel.2023.1242828\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T09:26:50Z","timestamp":1694683610000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fncel.2023.1242828\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,14]]},"references-count":65,"alternative-id":["10.3389\/fncel.2023.1242828"],"URL":"https:\/\/doi.org\/10.3389\/fncel.2023.1242828","relation":{},"ISSN":["1662-5102"],"issn-type":[{"value":"1662-5102","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,14]]},"article-number":"1242828"}}