{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T14:35:56Z","timestamp":1793802956747,"version":"4.6.1"},"reference-count":57,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,4,7]],"date-time":"2024-04-07T00:00:00Z","timestamp":1712448000000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82271370"],"award-info":[{"award-number":["82271370"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82371346"],"award-info":[{"award-number":["82371346"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>Mitochondria\u2010associated endoplasmic reticulum membranes (MAMs) serve as a crucial bridge connecting the endoplasmic reticulum (ER) and mitochondria within cells. Vesicle\u2010associated membrane protein\u2010associated protein B (VAPB) and protein tyrosine phosphatase interacting protein 51 (PTPIP51) are responsible for the formation and stability of MAMs, which have been implicated in the pathogenesis of various diseases. However, the role of MAMs in ischemic stroke (IS) remains unclear. We aimed to investigate the role of MAMs tethering protein VAPB\u2010PTPIP51 in experimental cerebral ischemia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We simulated cerebral ischemia\u2013reperfusion injury (CIRI) by using a mouse middle cerebral artery occlusion (MCAO) model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We observed a decrease in VAPB\u2010PTPIP51 expression in the brain tissue. Our findings suggested compromised MAMs after MCAO, as a decreased mitochondria\u2013ER contact (MERC) coverage and an increased distance were observed through the transmission electron microscope (TEM). Upon VAPB or PTPIP51 knockdown, the damage to MAMs was exacerbated, accompanied by excessive autophagy activation and increased reactive oxygen species (ROS) production, resulting in an enlarged infarct area and exacerbated neurological deficits. Notably, we observed that this damage was concomitant with the inhibition of the PI3K\/AKT\/mTOR pathway and was successfully mitigated by the treatment with the PI3K activator.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings suggest that the downregulation of VAPB\u2010PTPIP51 expression after IS mediates structural damage to MAMs. This may exacerbate CIRI by inhibiting the PI3K pathway and activating autophagy, thus providing new therapeutic targets for IS.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.14707","type":"journal-article","created":{"date-parts":[[2024,4,8]],"date-time":"2024-04-08T04:08:05Z","timestamp":1712549285000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Mitochondria\u2010associated endoplasmic reticulum membranes tethering protein VAPB\u2010PTPIP51 protects against ischemic stroke through inhibiting the activation of autophagy"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9283-4384","authenticated-orcid":false,"given":"Mingyang","family":"Li","sequence":"first","affiliation":[{"name":"Department of Neurosurgery Renmin Hospital of Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonggang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Renmin Hospital of Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guixiang","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Renmin Hospital of Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1928-8772","authenticated-orcid":false,"given":"Lijuan","family":"Gu","sequence":"additional","affiliation":[{"name":"Central Laboratory Renmin Hospital of Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Renmin Hospital of Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Renmin Hospital of Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6983-8547","authenticated-orcid":false,"given":"Xiaoxing","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Renmin Hospital of Wuhan University  Wuhan China"},{"name":"Central Laboratory Renmin Hospital of Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9150-5789","authenticated-orcid":false,"given":"Zhihong","family":"Jian","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Renmin Hospital of Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,4,7]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1474-4422(21)00252-0"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1474-4422(18)30233-3"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/str.0000000000000375"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.h56"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-022-01129-1"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)30962-X"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-022-01064-1"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200604016"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3440"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2018.03.002"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.04.010"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neures.2020.04.007"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.aat5185"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.11.094"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddr559"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.euroneuro.2020.08.010"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abh3763"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.ircmb.2019.11.002"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2020.102343"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41421-023-00576-6"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-006-8882-9"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2016.12.038"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12264-018-0276-9"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.15252\/embr.202051323"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-019-0688-4"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.280.5370.1763"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2010.06.029"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201006159"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-02-486217"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2022.115011"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2020.105020"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.950767"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.714943"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12975-022-01118-0"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.115.008897"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.112.656611"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10092177"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2020.8231"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14071637"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2023.154845"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1184429"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000013115"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10030657"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20200844"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-016-0140-8"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-024-01742-x"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-cellbio-092910-154005"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11910"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-018-0052-8"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.10.001"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2017.05.003"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2021.5011"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/nly119"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-019-10257-8"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10565-016-9345-x"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.204256"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12842"}],"container-title":["CNS Neuroscience &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cns.14707","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,29]],"date-time":"2024-05-29T03:58:41Z","timestamp":1716955121000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cns.14707"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4]]},"references-count":57,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2024,4]]}},"alternative-id":["10.1111\/cns.14707"],"URL":"https:\/\/doi.org\/10.1111\/cns.14707","archive":["Portico"],"relation":{},"ISSN":["1755-5930","1755-5949"],"issn-type":[{"value":"1755-5930","type":"print"},{"value":"1755-5949","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4]]},"assertion":[{"value":"2024-01-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-24","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-07","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e14707"}}