{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:12:48Z","timestamp":1787015568243,"version":"build-2736575974"},"reference-count":70,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,1,12]],"date-time":"2018-01-12T00:00:00Z","timestamp":1515715200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["126000"],"award-info":[{"award-number":["126000"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["136930"],"award-info":[{"award-number":["136930"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["89919"],"award-info":[{"award-number":["89919"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2018,4]]},"abstract":"Abstract<\/jats:title>\n \n \n \n Stress\u2010inducible phosphoprotein 1 (\n STI<\/jats:styled-content>\n 1) acts as a neuroprotective factor in the ischemic brain and its levels are increased following ischemia. Previous work has suggested that some of these\n STI<\/jats:styled-content>\n 1 actions in a stroke model depend on the recruitment of bone marrow\u2010derived stem cells to improve outcomes after ischemic insult. However,\n STI<\/jats:styled-content>\n 1 can directly increase neuroprotective signaling in neurons by engaging with the cellular prion protein (Pr\n \n P\n C<\/jats:sup>\n <\/jats:styled-content>\n ) and activating \u03b17 nicotinic acetylcholine receptors (\u03b17n\n AC<\/jats:styled-content>\n hR). Given that \u03b17n\n AC<\/jats:styled-content>\n hR activation has also been involved in neuroprotection in stroke, it is possible that\n STI<\/jats:styled-content>\n 1 can have direct actions on neurons to prevent deleterious consequences of ischemic insults. Here, we tested this hypothesis by exposing primary neuronal cultures to 1\u2010h oxygen\u2010glucose deprivation (\n OGD<\/jats:styled-content>\n ) and reperfusion and assessing signaling pathways activated by\n STI<\/jats:styled-content>\n 1\/Pr\n \n P\n C<\/jats:sup>\n <\/jats:styled-content>\n . Our results demonstrated that\n STI<\/jats:styled-content>\n 1 treatment significantly decreased apoptosis and cell death in mouse neurons submitted to\n OGD<\/jats:styled-content>\n in a manner that was dependent on Pr\n \n P\n C<\/jats:sup>\n <\/jats:styled-content>\n and \u03b17n\n AC<\/jats:styled-content>\n hR, but also on the activin A receptor 1 (\n ALK<\/jats:styled-content>\n 2), which has emerged as a signaling partner of\n STI<\/jats:styled-content>\n 1. Interestingly, pharmacological inhibition of the\n ALK<\/jats:styled-content>\n 2 receptor prevented neuroprotection by\n STI<\/jats:styled-content>\n 1, while activation of\n ALK<\/jats:styled-content>\n 2 receptors by bone morphogenetic protein 4 (\n BMP<\/jats:styled-content>\n 4) either before or after\n OGD<\/jats:styled-content>\n was effective in decreasing neuronal death induced by ischemia. We conclude that Pr\n \n P\n C<\/jats:sup>\n <\/jats:styled-content>\n \/\n STI<\/jats:styled-content>\n 1 engagement and its subsequent downstream signaling cascades involving \u03b17n\n AC<\/jats:styled-content>\n hR as well as the\n ALK<\/jats:styled-content>\n 2 receptor may be activated in neurons by increased levels of\n STI<\/jats:styled-content>\n 1. This signaling pathway protects neurons from ischemic insults.\n <\/jats:p>\n <\/jats:sec>\n \n \n \n \n \n image<\/jats:alt-text>\n <\/jats:graphic>\n <\/jats:boxed-text>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/jnc.14281","type":"journal-article","created":{"date-parts":[[2017,12,18]],"date-time":"2017-12-18T13:52:38Z","timestamp":1513605158000},"page":"68-79","source":"Crossref","is-referenced-by-count":17,"title":["Mechanisms of neuroprotection against ischemic insult by stress\u2010inducible phosphoprotein\u20101\/prion protein complex"],"prefix":"10.1111","volume":"145","author":[{"given":"Flavio H.","family":"Beraldo","sequence":"first","affiliation":[{"name":"Department of Physiology and Pharmacology Schulich School of Medicine and Dentistry University of Western Ontario London Ontario Canada"},{"name":"Robarts Research Institute Schulich School of Medicine and Dentistry University of Western Ontario London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeriy G.","family":"Ostapchenko","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology Schulich School of Medicine and Dentistry University of Western Ontario London Ontario Canada"},{"name":"Robarts Research Institute Schulich School of Medicine and Dentistry University of Western Ontario London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason Z.","family":"Xu","sequence":"additional","affiliation":[{"name":"Robarts Research Institute Schulich School of Medicine and Dentistry University of Western Ontario London Ontario Canada"},{"name":"Department of Anatomy & Cell Biology Schulich School of Medicine and Dentistry University of Western Ontario London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianni M.","family":"Di Guglielmo","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology Schulich School of Medicine and Dentistry University of Western Ontario London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jue","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Anatomy & Cell Biology Schulich School of Medicine and Dentistry University of Western Ontario London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Nicholls","sequence":"additional","affiliation":[{"name":"Psychiatry & Behavioral Sciences Duke University Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc G.","family":"Caron","sequence":"additional","affiliation":[{"name":"Department of Cell Biology Duke University Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vania F.","family":"Prado","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology Schulich School of Medicine and Dentistry University of Western Ontario London Ontario Canada"},{"name":"Robarts Research Institute Schulich School of Medicine and Dentistry University of Western Ontario London Ontario Canada"},{"name":"Department of Anatomy & Cell Biology Schulich School of Medicine and Dentistry University of Western Ontario London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3028-5778","authenticated-orcid":false,"given":"Marco A. 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