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Integr. Neurosci."],"abstract":"<jats:p>Background:Stroke is a major cause of morbidity and mortality, characterized by neuronal damage and complex cell death pathways. This study aimed to investigate the protective role of spermine oxidase (Smox) in ischemic stroke and its effect on neuronal autophagy.Methods:We employed transient middle cerebral artery occlusion (tMCAO) models and oxygen-glucose deprivation\/reoxygenation (OGD\/R) experiments in HT22 cells to explore the protective effects of Smox knockdown against ischemic injury and to evaluate changes in autophagy.Results:Smox levels were significantly elevated following stroke, and correlated with increased autophagic activity and neuronal apoptosis. In contrast, knockdown of Smox reduced neuronal death and improved neurological function while decreasing autophagy activation. Mechanistically, Smox may regulate autophagy via the phosphorylation of protein kinase B (AKT), AMP-activated protein kinase (AMPK), and mechanistic target of rapamycin (mTOR); Smox knockdown increased AKT and mTOR phosphorylation, while reducing AMPK phosphorylation, suggesting a potential shift in the regulation of neuronal autophagy.Conclusions:Our findings suggest a dual role for Smox in stroke pathology, indicating that it may influence autophagy via the AKT\/AMPK\/mTOR signaling, which could be critical for neuronal survival after ischemic injury. Targeting Smox may offer a therapeutic strategy for neuronal protection and recovery in stroke management, suggesting the potential importance of autophagy modulation in ischemic brain injury.<\/jats:p>","DOI":"10.31083\/jin50711","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:01:26Z","timestamp":1785409286000},"source":"Crossref","is-referenced-by-count":0,"title":["Knockdown of Smox Protects Against Cerebral Ischemia\/Reperfusion Injury by Suppressing Neuronal Autophagy via the AKT\/AMPK\/mTOR Phosphorylation Pathway"],"prefix":"10.31083","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6774-4755","authenticated-orcid":true,"given":"Zhihui","family":"Li","sequence":"first","affiliation":[{"name":"Department of Neurology, The Fourth Affiliated Hospital of Harbin Medical University, 150086 Harbin, Heilongjiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5280-1176","authenticated-orcid":true,"given":"Qian","family":"Wang","sequence":"additional","affiliation":[{"name":"Teaching Center of Pathogenic Biology, School of Basic Medical Sciences, Harbin Medical University, 150081 Harbin, Heilongjiang, China"},{"name":"Department of Microbiology, School of Basic Medical Sciences, Harbin Medical University, 150081 Harbin, Heilongjiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2205-2476","authenticated-orcid":true,"given":"Kaixuan","family":"Ma","sequence":"additional","affiliation":[{"name":"Teaching Center of Pathogenic Biology, School of Basic Medical Sciences, Harbin Medical University, 150081 Harbin, Heilongjiang, China"},{"name":"Department of Microbiology, School of Basic Medical Sciences, Harbin Medical University, 150081 Harbin, Heilongjiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3337-9604","authenticated-orcid":true,"given":"Mengna","family":"Yu","sequence":"additional","affiliation":[{"name":"Teaching Center of Pathogenic Biology, School of Basic Medical Sciences, Harbin Medical University, 150081 Harbin, Heilongjiang, China"},{"name":"Department of Microbiology, School of Basic Medical Sciences, Harbin Medical University, 150081 Harbin, Heilongjiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7729-5793","authenticated-orcid":true,"given":"Yanyan","family":"Wang","sequence":"additional","affiliation":[{"name":"Teaching Center of Morphology, School of Basic Medical Sciences, Harbin Medical University, 150081 Harbin, Heilongjiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6880-0626","authenticated-orcid":true,"given":"Zhongqiao","family":"Ge","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Harbin Medical University, 150081 Harbin, Heilongjiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3734-7428","authenticated-orcid":true,"given":"Peng","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Harbin Medical University, 150081 Harbin, Heilongjiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6191-7266","authenticated-orcid":true,"given":"Hui","family":"Wang","sequence":"additional","affiliation":[{"name":"Teaching Center of Pathogenic Biology, School of Basic Medical Sciences, Harbin Medical University, 150081 Harbin, Heilongjiang, China"},{"name":"Department of Microbiology, School of Basic Medical Sciences, Harbin Medical University, 150081 Harbin, Heilongjiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3404-2180","authenticated-orcid":true,"given":"Lexun","family":"Lin","sequence":"additional","affiliation":[{"name":"Teaching Center of Pathogenic Biology, School of Basic Medical Sciences, Harbin Medical University, 150081 Harbin, Heilongjiang, China"},{"name":"Department of Microbiology, School of Basic Medical Sciences, Harbin Medical University, 150081 Harbin, Heilongjiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2964-5404","authenticated-orcid":true,"given":"Yang","family":"Chen","sequence":"additional","affiliation":[{"name":"Teaching Center of Pathogenic Biology, School of Basic Medical Sciences, Harbin Medical University, 150081 Harbin, Heilongjiang, China"},{"name":"Department of Microbiology, School of Basic Medical Sciences, Harbin Medical University, 150081 Harbin, Heilongjiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2399-1699","authenticated-orcid":true,"given":"Lina","family":"Jia","sequence":"additional","affiliation":[{"name":"Teaching Center of Pathogenic Biology, School of Basic Medical Sciences, Harbin Medical University, 150081 Harbin, Heilongjiang, China"},{"name":"Department of Microbiology, School of Basic Medical Sciences, Harbin Medical University, 150081 Harbin, Heilongjiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0295-2819","authenticated-orcid":true,"given":"Heming","family":"Li","sequence":"additional","affiliation":[{"name":"Teaching Center of Pathogenic Biology, School of Basic Medical Sciences, Harbin Medical University, 150081 Harbin, 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