{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T06:21:57Z","timestamp":1791354117778,"version":"4.3.1"},"reference-count":19,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2015,10,26]],"date-time":"2015-10-26T00:00:00Z","timestamp":1445817600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Singapore's Agency for Science, Technology and Research"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Parasite Immunology"],"published-print":{"date-parts":[[2015,11]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Aside from antimalarials, there is currently no treatment for cerebral malaria, a fulminant neurological complication of <jats:italic>P.\u00a0falciparum<\/jats:italic> infection that is a leading cause of death in African children. In the mouse model of cerebral malaria, cross\u2010presentation of parasite antigens by brain endothelial cells is thought to be a crucial late step in pathogenesis. We have investigated three proteasome inhibitors as potential adjunct therapies: bortezomib, carfilzomib and <jats:styled-content style=\"fixed-case\">ONX<\/jats:styled-content>\u20100914. Only carfilzomib, an irreversible inhibitor of both constitutive proteasomes and immunoproteasomes, was able to inhibit cross\u2010presentation of malaria antigen by murine brain endothelial cells <jats:italic>in\u00a0vitro<\/jats:italic>. To mimic the clinical setting, carfilzomib was co\u2010administered with artesunate only when infected mice exhibited neurological defects. However, there was no improvement in survival compared to artesunate monotherapy. The treatment failure was explained by the inability of daily or twice daily bolus doses of carfilzomib to inhibit cross\u2010presentation by brain endothelial cells <jats:italic>in\u00a0vivo<\/jats:italic>. We also report here that bortezomib, which has been associated with neurological adverse events, accelerated death in <jats:styled-content style=\"fixed-case\">ECM<\/jats:styled-content>\u2010infected mice. Future investigations of proteasome inhibitors for modulating cross\u2010presentation during malaria infection should focus on sustained and targeted delivery to brain endothelial cells.<\/jats:p>","DOI":"10.1111\/pim.12277","type":"journal-article","created":{"date-parts":[[2015,9,14]],"date-time":"2015-09-14T15:09:02Z","timestamp":1442243342000},"page":"599-604","source":"Crossref","is-referenced-by-count":6,"title":["Investigating proteasome inhibitors as potential adjunct therapies for experimental cerebral malaria"],"prefix":"10.1111","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4794-1564","authenticated-orcid":false,"given":"S. W.","family":"Howland","sequence":"first","affiliation":[{"name":"Singapore Immunology Network Agency for Science, Technology and Research (A*STAR) Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. X. P.","family":"Ng","sequence":"additional","affiliation":[{"name":"Singapore Immunology Network Agency for Science, Technology and Research (A*STAR) Singapore"},{"name":"Department of Microbiology Yong Loo Lin School of Medicine National University of Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. K.","family":"Chia","sequence":"additional","affiliation":[{"name":"Singapore Immunology Network Agency for Science, Technology and Research (A*STAR) Singapore"},{"name":"School of Biological Sciences Nanyang Technological University Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"R\u00e9nia","sequence":"additional","affiliation":[{"name":"Singapore Immunology Network Agency for Science, Technology and Research (A*STAR) Singapore"},{"name":"Department of Microbiology Yong Loo Lin School of Medicine National University of Singapore Singapore"},{"name":"School of Biological Sciences Nanyang Technological University Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,10,26]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2014.00104"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)61924-1"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-10-23"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-015-0476-6"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004963"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/emmm.201202273"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.2174\/1381612811319220018"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.1978"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.1150"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.202445099"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-06-1768"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0903182"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-4086"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-01-065888"},{"key":"e_1_2_7_16_1","first-page":"4996","article-title":"Proteasome inhibitor PS\u2010341 inhibits human myeloma cell growth in\u00a0vivo and prolongs survival in a murine model","volume":"62","author":"LeBlanc R","year":"2002","journal-title":"Cancer Res"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.111.039164"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-7-187"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/1472-6904-7-13"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-10-1950"}],"container-title":["Parasite Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fpim.12277","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/pim.12277","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T22:28:53Z","timestamp":1696026533000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/pim.12277"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,10,26]]},"references-count":19,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2015,11]]}},"alternative-id":["10.1111\/pim.12277"],"URL":"https:\/\/doi.org\/10.1111\/pim.12277","archive":["Portico"],"relation":{},"ISSN":["0141-9838","1365-3024"],"issn-type":[{"value":"0141-9838","type":"print"},{"value":"1365-3024","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,10,26]]}}}