{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T12:48:13Z","timestamp":1792154893508,"version":"4.4.0"},"reference-count":24,"publisher":"National Academy of Sciences","issue":"23","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2009,6,9]]},"abstract":"<jats:p>\n                    Nematode parasitism is a worldwide health problem resulting in malnutrition and morbidity in over 1 billion people. The molecular mechanisms governing infection are poorly understood. Here, we report that an evolutionarily conserved nuclear hormone receptor signaling pathway governs development of the stage 3 infective larvae (iL3) in several nematode parasites, including\n                    <jats:italic>Strongyloides stercoralis, Ancylostoma spp.<\/jats:italic>\n                    , and\n                    <jats:italic>Necator americanus<\/jats:italic>\n                    . As in the free-living\n                    <jats:italic>Caenorhabditis elegans<\/jats:italic>\n                    , steroid hormone-like dafachronic acids induced recovery of the dauer-like iL3 in parasitic nematodes by activating orthologs of the nuclear receptor DAF-12. Moreover, administration of dafachronic acid markedly reduced the pathogenic iL3 population in\n                    <jats:italic>S. stercoralis<\/jats:italic>\n                    , indicating the potential use of DAF-12 ligands to treat disseminated strongyloidiasis. To understand the pharmacology of targeting DAF-12, we solved the 3-dimensional structure of the\n                    <jats:italic>S. stercoralis<\/jats:italic>\n                    DAF-12 ligand-binding domain cocrystallized with dafachronic acids. These results reveal the molecular basis for DAF-12 ligand binding and identify nuclear receptors as unique therapeutic targets in parasitic nematodes.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0904064106","type":"journal-article","created":{"date-parts":[[2009,6,4]],"date-time":"2009-06-04T17:35:13Z","timestamp":1244136913000},"page":"9138-9143","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":120,"title":["Identification of the nuclear receptor DAF-12 as a therapeutic target in parasitic nematodes"],"prefix":"10.1073","volume":"106","author":[{"given":"Zhu","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Howard Hughes Medical Institute, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"X. Edward","family":"Zhou","sequence":"additional","affiliation":[{"name":"Laboratory of Structural Sciences, Van Andel Research Institute, 333 Bostwick Avenue Northeast, Grand Rapids, MI 49503;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel L.","family":"Motola","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Howard Hughes Medical Institute, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Tropical Medicine, The George Washington University Medical Center, Ross Hall 705, 2300 I Street NW, Washington, DC 20037;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly","family":"Suino-Powell","sequence":"additional","affiliation":[{"name":"Laboratory of Structural Sciences, Van Andel Research Institute, 333 Bostwick Avenue Northeast, Grand Rapids, MI 49503;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aoife","family":"Conneely","sequence":"additional","affiliation":[{"name":"Laboratory of Structural Sciences, Van Andel Research Institute, 333 Bostwick Avenue Northeast, Grand Rapids, MI 49503;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig","family":"Ogata","sequence":"additional","affiliation":[{"name":"General Medicine and Cancer Institutes Collaborative Access Team, Building 436, D003, Argonne National Laboratory, 9700 South Cass Avenue, Argonne, IL 60439;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamalesh K.","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J.","family":"Auchus","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James B.","family":"Lok","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, 3800 Spruce Street, Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M.","family":"Hawdon","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Tropical Medicine, The George Washington University Medical Center, Ross Hall 705, 2300 I Street NW, Washington, DC 20037;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven A.","family":"Kliewer","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Howard Hughes Medical Institute, and"},{"name":"Department of Molecular Biology, University of Texas Southwestern Medical Center, 6001 Forest Park Road, Dallas, TX 75390;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. Eric","family":"Xu","sequence":"additional","affiliation":[{"name":"Laboratory of Structural Sciences, Van Andel Research Institute, 333 Bostwick Avenue Northeast, Grand Rapids, MI 49503;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Mangelsdorf","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Howard Hughes Medical Institute, and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2009,6,9]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.phyto.41.052102.104023"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2006.05.004"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/3.3.397"},{"key":"e_1_3_3_4_2","volume-title":"Strongyloides spp. WormBook","author":"Viney ME","year":"2007","unstructured":"ME Viney, JB Lok Strongyloides spp. WormBook, doi\/10.1895\/wormbook.1.141.1, http:\/\/www.wormbook.org. 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