{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T12:35:40Z","timestamp":1786365340214,"version":"build-2736575974"},"reference-count":61,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2015,1,1]],"date-time":"2015-01-01T00:00:00Z","timestamp":1420070400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2015,1,1]],"date-time":"2015-01-01T00:00:00Z","timestamp":1420070400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antioxidants &amp; Redox Signaling"],"published-print":{"date-parts":[[2015,1]]},"abstract":"<jats:p>\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Aims:<\/jats:italic>\n                    <\/jats:bold>\n                    Pharmacological activation of the adaptive response to hypoxia is a therapeutic strategy of growing interest for neurological conditions, including stroke, Huntington's disease, and Parkinson's disease. We screened a drug library with known safety in humans using a hippocampal neuroblast line expressing a reporter of hypoxia-inducible factor (HIF)-dependent transcription.\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Results:<\/jats:italic>\n                    <\/jats:bold>\n                    Our screen identified more than 40 compounds with the ability to induce hypoxia response element-driven luciferase activity as well or better than deferoxamine, a canonical activator of hypoxic adaptation. Among the chemical entities identified, the antihelminthic benzimidazoles represented one pharmacophore that appeared multiple times in our screen. Secondary assays confirmed that antihelminthics stabilized the transcriptional activator HIF-1\u03b1 and induced expression of a known HIF target gene,\n                    <jats:italic toggle=\"yes\">\n                      p21\n                      <jats:sup>cip1\/waf1<\/jats:sup>\n                    <\/jats:italic>\n                    , in post-mitotic cortical neurons. The on-target effect of these agents in stimulating hypoxic signaling was binding to free tubulin. Moreover, antihelminthic benzimidazoles also abrogated oxidative stress-induced death\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    , and this on-target effect also involves binding to free tubulin.\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Innovation and Conclusions:<\/jats:italic>\n                    <\/jats:bold>\n                    These studies demonstrate that tubulin-binding drugs can activate a component of the hypoxic adaptive response, specifically the stabilization of HIF-1\u03b1 and its downstream targets. Tubulin-binding drugs, including antihelminthic benzimidazoles, also abrogate oxidative neuronal death in primary neurons. Given their safety in humans and known ability to penetrate into the central nervous system, antihelminthic benzimidazoles may be considered viable candidates for treating diseases associated with oxidative neuronal death, including stroke.\n                    <jats:italic toggle=\"yes\">Antioxid. Redox Signal.<\/jats:italic>\n                    22, 121\u2013134.\n                  <\/jats:p>","DOI":"10.1089\/ars.2013.5595","type":"journal-article","created":{"date-parts":[[2014,4,26]],"date-time":"2014-04-26T22:37:05Z","timestamp":1398551825000},"page":"121-134","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":21,"title":["Antihelminthic Benzimidazoles Are Novel HIF Activators That Prevent Oxidative Neuronal Death\n                    <i>via<\/i>\n                    Binding to Tubulin"],"prefix":"10.1177","volume":"22","author":[{"given":"Hossein","family":"Aleyasin","sequence":"first","affiliation":[{"name":"Burke-Cornell Medical Research Institute"},{"name":"Weill Medical College of Cornell University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saravanan S.","family":"Karuppagounder","sequence":"additional","affiliation":[{"name":"Burke-Cornell Medical Research 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