{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T11:27:17Z","timestamp":1790767637438,"version":"4.1.0"},"reference-count":50,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>The ubiquitin-proteasome system (UPS) and autophagy are 2 major protein degradation pathways in eukaryotic cells. We previously identified a switch from UPS to autophagy with changes in BAG3 (B-cell lymphoma 2-associated-athanogene 3) expression after cerebral ischemia in mice. BAG3 is an antiapoptotic-cochaperone that is directly involved in cellular protein quality control as a mediator for selective macroautophagy. Here, we aimed to investigate the role of BAG3 in ischemic stroke.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>Middle cerebral artery occlusion\/reperfusion (MCAO\/R) and oxygen-glucose deprivation\/reoxygenation were used to mimic cerebral ischemia in vivo and in vitro. The UPS inhibitor MG132 and autophagy inhibitor 3-MA (3-methyladenine) were administered to mice to identify how BAG3 was involved after MCAO\/R. Adeno-associated virus and lentiviral vector were used to regulate BAG3 expression in vivo and in vitro, respectively. Behavioral tests, 2,3,5-triphenyltetrazolium chloride staining, and Hematoxylin &amp; Eosin staining were performed to evaluate cerebral injury following MCAO\/R, and a Cell Counting kit-8 assay was conducted to assess oxygen-glucose deprivation\/reoxygenation\u2013induced injury in cells. Brain tissues and cell lysates were collected and analyzed for UPS activation, autophagy, and apoptosis.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>The UPS inhibitor alleviated MCAO injury in mice and increased autophagy and BAG3 expression, whereas the autophagy inhibitor exacerbated MCAO\/R-induced injury. In addition, BAG3 overexpression significantly improved neurological outcomes, reduced infarct volume in vivo, and enhanced cell survival by activating autophagy and suppressing apoptosis in vitro.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>Our findings indicate that BAG3 overexpression activates autophagy and inhibits apoptosis to prevent cerebral ischemia\/reperfusion and hypoxia\/reoxygenation injury, suggesting a potential therapeutic benefit of BAG3 expression in cerebral ischemia.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/strokeaha.123.041783","type":"journal-article","created":{"date-parts":[[2023,6,28]],"date-time":"2023-06-28T13:01:17Z","timestamp":1687957277000},"page":"2114-2125","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":73,"title":["BAG3 Overexpression Attenuates Ischemic Stroke Injury by Activating Autophagy and Inhibiting Apoptosis"],"prefix":"10.1161","volume":"54","author":[{"given":"Xia","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Neurology (Xia Liu, Z.H., X. Li, L.Z., Xuan Liu, L.R.), The First Affiliated Hospital of Shenzhen University, Shenzhen Second People\u2019s Hospital, China."},{"name":"Department of Neurology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, China (Xia Liu, Y.-C.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinlian","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The Institute Translational Medicine (Q.Y., Y.-C.W.), The First Affiliated Hospital of Shenzhen University, Shenzhen Second People\u2019s Hospital, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0196-5109","authenticated-orcid":true,"given":"Zhengzheng","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Neurology (Xia Liu, Z.H., X. Li, L.Z., Xuan Liu, L.R.), The First Affiliated Hospital of Shenzhen University, Shenzhen Second People\u2019s Hospital, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuping","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology (Xia Liu, Z.H., X. Li, L.Z., Xuan Liu, L.R.), The First Affiliated Hospital of Shenzhen University, Shenzhen Second People\u2019s Hospital, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology (Xia Liu, Z.H., X. Li, L.Z., Xuan Liu, L.R.), The First Affiliated Hospital of Shenzhen University, Shenzhen Second People\u2019s Hospital, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9883-4289","authenticated-orcid":true,"given":"Xuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology (Xia Liu, Z.H., X. 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