{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T01:52:17Z","timestamp":1784771537508,"version":"3.55.0"},"reference-count":68,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2020,10,2]],"date-time":"2020-10-02T00:00:00Z","timestamp":1601596800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004586","name":"Funda\u00e7\u00e3o Carlos Chagas Filho de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro","doi-asserted-by":"publisher","award":["E-26\/202.359\/2017"],"award-info":[{"award-number":["E-26\/202.359\/2017"]}],"id":[{"id":"10.13039\/501100004586","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The ENA ATPases (from exitus natru: the exit of sodium) belonging to the P-type ATPases are structurally very similar to the sarco\/endoplasmic reticulum Ca2+-ATPase (SERCA); they exchange Na+ for H+ and, therefore, are also known as Na+-ATPases. ENA ATPases are required in alkaline milieu, as in the case for Aspergillus, where other transporters cannot mediate an uphill Na+ efflux. They are also important for salt tolerance, as described for Arabidopsis. During their life cycles, protozoan parasites might encounter a high pH environment, thus allowing consideration of ENA ATPases as possible targets for controlling certain severe parasitic diseases, such as Chagas\u2019 Disease. Phylogenetic analysis has now shown that, besides the types IIA, IIB, IIC, and IID P-type ATPases, there exists a 5th subgroup of ATPases classified as ATP4-type ATPases, found in Plasmodium falciparum and Toxoplasma gondii. In malaria, for example, some drugs targeting PfATP4 destroy Na+ homeostasis; these drugs, which include spiroindolones, are now in clinical trials. The ENA P-type (IID P-type ATPase) and ATP4-type ATPases have no structural homologue in mammalian cells, appearing only in fungi, plants, and protozoan parasites, e.g., Trypanosoma cruzi, Leishmania sp., Toxoplasma gondii, and Plasmodium falciparum. This exclusivity makes Na+-ATPase a potential candidate for the biologically-based design of new therapeutic interventions; for this reason, Na+-ATPases deserves more attention.<\/jats:p>","DOI":"10.3390\/cells9102225","type":"journal-article","created":{"date-parts":[[2020,10,2]],"date-time":"2020-10-02T09:39:25Z","timestamp":1601631565000},"page":"2225","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["The Functioning of Na+-ATPases from Protozoan Parasites: Are These Pumps Targets for Antiparasitic Drugs?"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2251-6409","authenticated-orcid":false,"given":"Claudia F.","family":"Dick","sequence":"first","affiliation":[{"name":"Leopoldo de Meis Institute of Medical Biochemistry, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil"},{"name":"Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro 21941-170, Brazil"},{"name":"National Center of Structural Biology and Bioimaging\/CENABIO, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Roberto","family":"Meyer-Fernandes","sequence":"additional","affiliation":[{"name":"Leopoldo de Meis Institute of Medical Biochemistry, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil"},{"name":"National Center of Structural Biology and Bioimaging\/CENABIO, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8009-7273","authenticated-orcid":false,"given":"Adalberto","family":"Vieyra","sequence":"additional","affiliation":[{"name":"Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro 21941-170, Brazil"},{"name":"National Center of Structural Biology and Bioimaging\/CENABIO, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil"},{"name":"Graduate Programa of Translational Biomedicine\/BIOTRANS, Unigranrio University, Duque de Caxias 25071-202, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"F811","DOI":"10.1152\/ajprenal.00351.2003","article-title":"Kidneys sans glomeruli","volume":"286","author":"Beyenbach","year":"2004","journal-title":"Am. 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