{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T20:24:20Z","timestamp":1793391860759,"version":"4.5.0"},"reference-count":51,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,12,20]],"date-time":"2017-12-20T00:00:00Z","timestamp":1513728000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,12,20]],"date-time":"2017-12-20T00:00:00Z","timestamp":1513728000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The heat shock protein 90 (Hsp90) family of molecular chaperones regulates protein homeostasis, folding, and degradation. The ER-resident Hsp90 isoform, glucose-regulated protein 94 (Grp94), promotes the aggregation of mutant forms of myocilin, a protein associated with primary open-angle glaucoma. While inhibition of Grp94 promotes the degradation of mutant myocilin <jats:italic>in vitro<\/jats:italic>, to date no Grp94-selective inhibitors have been investigated <jats:italic>in vivo<\/jats:italic>. Here, a Grp94-selective inhibitor facilitated mutant myocilin degradation and rescued phenotypes in a transgenic mouse model of hereditary primary open-angle glaucoma. Ocular toxicities previously associated with pan-Hsp90 inhibitors were not evident with our Grp94-selective inhibitor, 4-Br-BnIm. Our study suggests that selective inhibition of a distinct Hsp90 family member holds translational promise for ocular and other diseases associated with cell stress and protein misfolding.<\/jats:p>","DOI":"10.1038\/s41598-017-18344-4","type":"journal-article","created":{"date-parts":[[2017,12,14]],"date-time":"2017-12-14T16:36:14Z","timestamp":1513269374000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Isoform-selective Hsp90 inhibition rescues model of hereditary open-angle glaucoma"],"prefix":"10.1038","volume":"7","author":[{"given":"Andrew R.","family":"Stothert","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amirthaa","family":"Suntharalingam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolan","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent M.","family":"Crowley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanket J.","family":"Mishra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack M.","family":"Webster","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryce A.","family":"Nordhues","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dustin J. E.","family":"Huard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher L.","family":"Passaglia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel L.","family":"Lieberman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian S. J.","family":"Blagg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4981-5564","authenticated-orcid":false,"given":"Laura J.","family":"Blair","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6017-1763","authenticated-orcid":false,"suffix":"III","given":"John","family":"Koren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3834-3159","authenticated-orcid":false,"given":"Chad A.","family":"Dickey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,12,20]]},"reference":[{"key":"18344_CR1","doi-asserted-by":"publisher","first-page":"1113","DOI":"10.1056\/NEJMra0804630","volume":"360","author":"YH Kwon","year":"2009","unstructured":"Kwon, Y. H., Fingert, J. H., Kuehn, M. H. & Alward, W. L. M. Primary open-angle glaucoma. N. Engl. J. Med. \n                           360, 1113\u20131124 (2009).","journal-title":"N. Engl. J. Med."},{"key":"18344_CR2","doi-asserted-by":"publisher","first-page":"1097","DOI":"10.1056\/NEJM199304153281507","volume":"328","author":"HA Quigley","year":"1993","unstructured":"Quigley, H. A. Open-angle glaucoma. N. Engl. J. Med. \n                           328, 1097\u20131106 (1993).","journal-title":"N. Engl. J. Med."},{"key":"18344_CR3","doi-asserted-by":"publisher","first-page":"1901","DOI":"10.1001\/jama.2014.3192","volume":"311","author":"RN Weinreb","year":"2014","unstructured":"Weinreb, R. N., Aung, T. & Medeiros, F. A. The Pathophysiology and Treatment of Glaucoma: A Review. 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