{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:58:59Z","timestamp":1760151539859,"version":"build-2065373602"},"reference-count":77,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,3,28]],"date-time":"2022-03-28T00:00:00Z","timestamp":1648425600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>M\u00e9ni\u00e8re\u2019s disease is a chronic illness characterized by intermittent episodes of vertigo associated with fluctuating sensorineural hearing loss, tinnitus and aural pressure. This pathology strongly correlates with a dilatation of the fluid compartment of the endolymph, so-called hydrops. Dexamethasone is one of the therapeutic approaches recommended when conventional antivertigo treatments have failed. Several mechanisms of actions have been hypothesized for the mode of action of dexamethasone, such as the anti-inflammatory effect or as a regulator of inner ear water homeostasis. However, none of them have been experimentally confirmed so far. Aquaporins (AQPs) are transmembrane water channels and are hence central in the regulation of transcellular water fluxes. In the present study, we investigated the hypothesis that dexamethasone could impact water fluxes in the inner ear by targeting AQP2. We addressed this question through molecular dynamics simulations approaches and managed to demonstrate a direct interaction between AQP2 and dexamethasone and its significant impact on the channel water permeability. Through compartmentalization of sodium and potassium ions, a significant effect of Na+ upon AQP2 water permeability was highlighted as well. The molecular mechanisms involved in dexamethasone binding and in its regulatory action upon AQP2 function are described.<\/jats:p>","DOI":"10.3390\/biom12040511","type":"journal-article","created":{"date-parts":[[2022,3,29]],"date-time":"2022-03-29T21:40:14Z","timestamp":1648590014000},"page":"511","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A Perspective for M\u00e9ni\u00e8re\u2019s Disease: In Silico Investigations of Dexamethasone as a Direct Modulator of AQP2"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0141-2651","authenticated-orcid":false,"given":"Robin","family":"Mom","sequence":"first","affiliation":[{"name":"Research Group on Vestibular Pathophysiology, CNRS, Unit GDR2074, F-13331 Marseille, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julien","family":"Robert-Paganin","sequence":"additional","affiliation":[{"name":"Structural Motility, Institut Curie, Paris Universit\u00e9 Sciences et Lettres, Sorbonne Universit\u00e9, CNRS UMR144, F-75005 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thierry","family":"Mom","sequence":"additional","affiliation":[{"name":"Research Group on Vestibular Pathophysiology, CNRS, Unit GDR2074, F-13331 Marseille, France"},{"name":"Service d\u2019ORL et de Chirurgie Cervicofaciale, H\u00f4pital Gabriel Montpied, F-63003 Clermont-Ferrand, France"},{"name":"Unit\u00e9 Mixte de Recherche (UMR) 1107 Neurodol, INSERM, F-63003 Clermont-Ferrand, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3932-0223","authenticated-orcid":false,"given":"Christian","family":"Chabbert","sequence":"additional","affiliation":[{"name":"Research Group on Vestibular Pathophysiology, CNRS, Unit GDR2074, F-13331 Marseille, France"},{"name":"Aix Marseille University-CNRS, Laboratory of Cognitive Neurosciences, Team Pathophysiology and Therapy of Vestibular Disorders, UMR7291, F-13331 Marseille, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2089-6727","authenticated-orcid":false,"given":"St\u00e9phane","family":"R\u00e9ty","sequence":"additional","affiliation":[{"name":"Laboratoire de Biologie et Mod\u00e9lisation de la Cellule, ENS de Lyon, University Claude Bernard, CNRS UMR 5239, INSERM U1210, 46 All\u00e9e d\u2019Italie Site Jacques Monod, F-69007 Lyon, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4713-9096","authenticated-orcid":false,"given":"Daniel","family":"Auguin","sequence":"additional","affiliation":[{"name":"Structural Motility, Institut Curie, Paris Universit\u00e9 Sciences et Lettres, Sorbonne Universit\u00e9, CNRS UMR144, F-75005 Paris, France"},{"name":"Laboratoire de Biologie des Ligneux et des Grandes Cultures, Universit\u00e9 d\u2019Orl\u00e9ans, UPRES EA 1207, INRA-USC1328, F-45067 Orl\u00e9ans, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,28]]},"reference":[{"unstructured":"M\u00e9ni\u00e8re, P. 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