{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T15:32:40Z","timestamp":1777044760013,"version":"3.51.4"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2024,12,20]],"date-time":"2024-12-20T00:00:00Z","timestamp":1734652800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Science and Technology Project of Jiangxi Health Commission","award":["202310021"],"award-info":[{"award-number":["202310021"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,2,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Ischemic strokes pose serious risks to human health. We aimed to elucidate the function of NOD-like receptor X1 (NLRX1) in a rat middle cerebral artery occlusion (MCAO)-induced cerebral ischemia\/reperfusion injury (CIRI) model and in an oxygen-glucose deprivation\/reperfusion (OGD\/R)-treated human microglial cell line (HMC3) model. Following NLRX1 upregulation, infarct volumes were measured with 2,3,5-triphenyltetrazolium chloride staining and pathological examination was conducted with hematoxylin-eosin staining. Results suggested that levels of NLRX1 were decreased in brain tissue of MCAO rats and in OGD\/R-stimulated HMC3 cells. NOD-like receptor X1 overexpression mitigated the neuronal damage, reduced tumor necrosis factor-\u03b1 and interleukin-6 expression, alleviated microglial activation, and induced autophagy in vivo and in vitro. Additionally, a coimmunoprecipitation assay indicated that NLRX1 bound to autophagy-related gene 5 (ATG5) to elevate ATG5 expression in HMC3 cells. Further, the elevated NLR family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD, and cleaved caspase 1 expression in MCAO rats and HMC3 cells with OGD\/R induction was reduced after NLRX1 upregulation. Importantly, ATG5 depletion abrogated the effects of NLRX1 elevation on NLRP3 inflammasome signaling. These results indicate that NLRX1 promotes autophagy and inactivates NLRP3 inflammasome signaling by binding ATG5 in experimental cerebral ischemia. These data may help the development of novel therapeutic strategies for ischemic stroke.<\/jats:p>","DOI":"10.1093\/jnen\/nlae129","type":"journal-article","created":{"date-parts":[[2024,12,21]],"date-time":"2024-12-21T04:34:30Z","timestamp":1734755670000},"page":"223-235","source":"Crossref","is-referenced-by-count":6,"title":["NOD-like receptor X1 promotes autophagy and inactivates NLR family pyrin domain containing 3 inflammasome signaling by binding autophagy-related gene 5 to alleviate cerebral ischemia\/reperfusion-induced neuronal injury"],"prefix":"10.1093","volume":"84","author":[{"given":"Yufen","family":"Peng","sequence":"first","affiliation":[{"name":"Department of Neurology, The First Affiliated Hospital of Nanchang University , Nanchang,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong","family":"Long","sequence":"additional","affiliation":[{"name":"Department of Neurology, The First Affiliated Hospital of Nanchang University , Nanchang,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chenyi","family":"Wan","sequence":"additional","affiliation":[{"name":"Department of Neurology, The First Affiliated Hospital of Nanchang University , Nanchang,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2024,12,20]]},"reference":[{"key":"2025022107522610100_nlae129-B1","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.mcna.2018.10.001","article-title":"Cerebrovascular disease: primary and secondary stroke prevention","volume":"103","author":"Caprio","year":"2019","journal-title":"Med Clin North Am"},{"key":"2025022107522610100_nlae129-B2","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1056\/NEJMc1900607","article-title":"Lifetime risk of stroke in the global burden of disease study","volume":"380","author":"Zhao","year":"2019","journal-title":"N Engl J 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