{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:42:32Z","timestamp":1792806152228,"version":"4.5.0"},"reference-count":115,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,6,29]],"date-time":"2023-06-29T00:00:00Z","timestamp":1687996800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Instituto Oswaldo Cruz, Funda\u00e7\u00e3o Oswaldo Cruz (FIOCRUZ)","award":["001"],"award-info":[{"award-number":["001"]}],"id":[{"id":"https:\/\/ror.org\/04jhswv08","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior (CAPES)","award":["001"],"award-info":[{"award-number":["001"]}],"id":[{"id":"https:\/\/ror.org\/00x0ma614","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Universidade Federal do Estado do Rio de Janeiro (UNIRIO)","award":["001"],"award-info":[{"award-number":["001"]}],"id":[{"id":"https:\/\/ror.org\/04tec8z30","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Funda\u00e7\u00e3o Carlos Chagas Filho de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro (FAPERJ)","award":["001"],"award-info":[{"award-number":["001"]}],"id":[{"id":"https:\/\/ror.org\/03kk0s825","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico (CNPq)","award":["001"],"award-info":[{"award-number":["001"]}],"id":[{"id":"https:\/\/ror.org\/03swz6y49","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Pontifical Catholic University of Rio de Janeiro (PUC-Rio)","award":["001"],"award-info":[{"award-number":["001"]}],"id":[{"id":"https:\/\/ror.org\/01dg47b60","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Inada and Ido identified Leptospira sp. as the pathogen responsible for Weil\u2019s Disease in 1915. Later, it was confirmed that Leptospira causes leptospirosis. The host microorganism\u2019s interaction at the cellular level remained misunderstood for many years. Although different bacterial components have been isolated and purified, the complexity of the molecular interactions between these components and the host and the molecular mechanisms responsible for the systemic dysfunctions still needs to be fully unveiled. Leptospirosis affects virtually all animal species. Its cellular pathophysiology must involve a ubiquitous cellular mechanism in all eukaryotes. Na\/K-ATPase is the molecular target of the leptospiral endotoxin (glycolipoprotein\u2014GLP). Na\/K-ATPase dysfunctions on different types of cells give rise to the organ disorders manifested in leptospirosis. Concomitantly, the development of a peculiar metabolic disorder characterized by dyslipidemia, with increased levels of circulating free fatty acids and an imbalance in the fatty acid\/albumin molar ratio, triggers events of cellular lipotoxicity. Synergistically, multiple molecular stimuli are prompted during the infection, activating inflammasomes and Na\/K-ATPase signalosome, leading to pro-inflammatory and metabolic alterations during leptospirosis. Leptospirosis involves diverse molecular mechanisms and alteration in patient inflammatory and metabolic status. Nonetheless, Na\/K-ATPase is critical in the disease, and it is targeted by GLP, its components, and other molecules, such as fatty acids, that inhibit or trigger intracellular signaling through this enzyme. Herein, we overview the role of Na\/K-ATPase during leptospirosis infection as a potential therapeutic target or an indicator of disease severity.<\/jats:p>","DOI":"10.3390\/microorganisms11071695","type":"journal-article","created":{"date-parts":[[2023,6,29]],"date-time":"2023-06-29T00:49:47Z","timestamp":1687999787000},"page":"1695","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Cellular Pathophysiology of Leptospirosis: Role of Na\/K-ATPase"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4458-3055","authenticated-orcid":false,"given":"Cassiano Felippe","family":"Gon\u00e7alves-de-Albuquerque","sequence":"first","affiliation":[{"name":"Laboratory of Immunopharmacology, Department of Physiology, Federal University of the State of Rio de Janeiro (UNIRIO), Rio de Janeiro 20211-030, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina Medina Coeli da","family":"Cunha","sequence":"additional","affiliation":[{"name":"Laboratory of Immunopharmacology, Department of Physiology, Federal University of the State of Rio de Janeiro (UNIRIO), Rio de Janeiro 20211-030, Brazil"},{"name":"Neuroscience Graduate Program, Federal Fluminense University (UFF), Niteroi 24000-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00e9o Victor Grimaldi de","family":"Castro","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Biology, Oswaldo Cruz Institute (IOC), Rio de Janeiro 21040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline de Azevedo","family":"Martins","sequence":"additional","affiliation":[{"name":"School of Medicine and Surgery, Federal University of the State of Rio de Janeiro (UNIRIO), Rio de Janeiro 20270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcos Roberto Colombo","family":"Barnese","sequence":"additional","affiliation":[{"name":"FISCLINEX Postgraduate Program, State University of Rio de Janeiro (UERJ), Rio de Janeiro 20550-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patr\u00edcia","family":"Burth","sequence":"additional","affiliation":[{"name":"Laboratory of Enzymology and Cellular Signaling, Department of Cellular and Molecular Biology, Federal Fluminense University (UFF), Niteroi 24000-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2521-764X","authenticated-orcid":false,"given":"Mauricio","family":"Younes-Ibrahim","sequence":"additional","affiliation":[{"name":"FISCLINEX Postgraduate Program, State University of Rio de Janeiro (UERJ), Rio de Janeiro 20550-900, Brazil"},{"name":"Department of Medicine, Pontifical Catholic University of Rio de Janeiro (PUC-Rio), Rio de Janeiro 22453-900, Brazil"},{"name":"State University of Rio de Janeiro (UERJ), Rio de Janeiro 20550-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Costa, F., Hagan, J.E., Calcagno, J., Kane, M., Torgerson, P., Martinez-Silveira, M.S., Stein, C., Abela-Ridder, B., and Ko, A.I. 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