{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:04:54Z","timestamp":1787317494754,"version":"build-2736575974"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T00:00:00Z","timestamp":1781827200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>\n                    African trypanosomiasis is a neglected disease affecting humans and animals in sub-Saharan Africa, caused by extracellular parasites of the\n                    <jats:italic>Trypanosoma brucei<\/jats:italic>\n                    species complex. Despite recent progress in disease control, current treatments are limited by toxicity, emerging resistance, and incomplete understanding of their mechanisms of action, highlighting the need for new targeted therapeutic strategies. In\n                    <jats:italic>Trypanosoma brucei<\/jats:italic>\n                    , post-translational modifications such as SUMOylation play essential roles in cellular processes, including cell cycle progression and variable surface antigen expression, making this pathway an attractive therapeutic target. We evaluated the effect of ML-792, a selective inhibitor of the SUMO-activating enzyme (E1, SAE), on bloodstream form parasites. Structural analysis showed conservation of key features of the E1 enzyme, consistent with susceptibility to inhibition. ML-792 treatment reduced global SUMO conjugation and nuclear SUMO levels and impaired parasite proliferation in a dose-dependent manner, with an IC\n                    <jats:sub>50<\/jats:sub>\n                    in the micromolar range, and induced defects in cell cycle progression, including abnormal nuclei\/kinetoplast configurations. These results demonstrate that pharmacological inhibition of SUMOylation disrupts essential processes in\n                    <jats:italic>T. brucei<\/jats:italic>\n                    and support the SUMO pathway as a potential target for therapeutic intervention.\n                  <\/jats:p>","DOI":"10.3389\/fcimb.2026.1850640","type":"journal-article","created":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T05:46:40Z","timestamp":1781848000000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["ML-792 impairs Trypanosoma brucei growth through SUMO pathway disruption: toward E1 as a candidate antitrypanosomal target"],"prefix":"10.3389","volume":"16","author":[{"given":"Emily Denise","family":"Fischman","sequence":"first","affiliation":[{"name":"Instituto de Investigaciones Biotecnol\u00f3gicas, Universidad Nacional de San Mart\u00edn (UNSAM) - Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET)","place":["San Martin, Argentina"]},{"name":"Escuela de Bio y Nanotecnolog\u00edas (EByN), Universidad Nacional de San Mart\u00edn","place":["San Martin, Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melina","family":"Serassio","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biotecnol\u00f3gicas, Universidad Nacional de San Mart\u00edn (UNSAM) - Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET)","place":["San Martin, Argentina"]},{"name":"Escuela de Bio y Nanotecnolog\u00edas (EByN), Universidad Nacional de San Mart\u00edn","place":["San Martin, Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanina Eder","family":"Alvarez","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biotecnol\u00f3gicas, Universidad Nacional de San Mart\u00edn (UNSAM) - Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET)","place":["San Martin, Argentina"]},{"name":"Escuela de Bio y Nanotecnolog\u00edas (EByN), Universidad Nacional de San Mart\u00edn","place":["San Martin, Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula Ana","family":"Iribarren","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biotecnol\u00f3gicas, Universidad Nacional de San Mart\u00edn (UNSAM) - Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET)","place":["San Martin, Argentina"]},{"name":"Escuela de Bio y Nanotecnolog\u00edas (EByN), Universidad Nacional de San Mart\u00edn","place":["San Martin, Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1038\/s41586-024-07487-w","article-title":"Accurate structure prediction of biomolecular interactions with AlphaFold 3","volume":"630","author":"Abramson","year":"2024","journal-title":"Nature"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0254558","article-title":"The potential economic benefits of controlling trypanosomiasis using waterbuck repellent blend in sub-Saharan Africa","volume":"16","author":"Abro","year":"2021","journal-title":"PloS One"},{"key":"B3","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.molbiopara.2004.10.002","article-title":"A doubly inducible system for RNA interference and rapid RNAi plasmid construction in Trypanosoma brucei","volume":"139","author":"Alibu","year":"2005","journal-title":"Mol. 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