A Perspective for Ménière’s Disease: In Silico Investigations of Dexamethasone as a Direct Modulator of AQP2
Ménière’s 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. Dexamethaso...
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| Format: | Article |
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MDPI AG
2022-03-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/12/4/511 |
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| author | Robin Mom Julien Robert-Paganin Thierry Mom Christian Chabbert Stéphane Réty Daniel Auguin |
| author_facet | Robin Mom Julien Robert-Paganin Thierry Mom Christian Chabbert Stéphane Réty Daniel Auguin |
| author_sort | Robin Mom |
| collection | DOAJ |
| description | Ménière’s 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. |
| first_indexed | 2024-03-09T11:06:18Z |
| format | Article |
| id | doaj.art-959f4e3f6c77463f836dbcc47c0d9497 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-09T11:06:18Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-959f4e3f6c77463f836dbcc47c0d94972023-12-01T00:55:36ZengMDPI AGBiomolecules2218-273X2022-03-0112451110.3390/biom12040511A Perspective for Ménière’s Disease: In Silico Investigations of Dexamethasone as a Direct Modulator of AQP2Robin Mom0Julien Robert-Paganin1Thierry Mom2Christian Chabbert3Stéphane Réty4Daniel Auguin5Research Group on Vestibular Pathophysiology, CNRS, Unit GDR2074, F-13331 Marseille, FranceStructural Motility, Institut Curie, Paris Université Sciences et Lettres, Sorbonne Université, CNRS UMR144, F-75005 Paris, FranceResearch Group on Vestibular Pathophysiology, CNRS, Unit GDR2074, F-13331 Marseille, FranceResearch Group on Vestibular Pathophysiology, CNRS, Unit GDR2074, F-13331 Marseille, FranceLaboratoire de Biologie et Modélisation de la Cellule, ENS de Lyon, University Claude Bernard, CNRS UMR 5239, INSERM U1210, 46 Allée d’Italie Site Jacques Monod, F-69007 Lyon, FranceStructural Motility, Institut Curie, Paris Université Sciences et Lettres, Sorbonne Université, CNRS UMR144, F-75005 Paris, FranceMénière’s 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.https://www.mdpi.com/2218-273X/12/4/511human AQP2dexamethasoneMénière’s diseasewater channelwater permeability modulationmolecular dynamics |
| spellingShingle | Robin Mom Julien Robert-Paganin Thierry Mom Christian Chabbert Stéphane Réty Daniel Auguin A Perspective for Ménière’s Disease: In Silico Investigations of Dexamethasone as a Direct Modulator of AQP2 Biomolecules human AQP2 dexamethasone Ménière’s disease water channel water permeability modulation molecular dynamics |
| title | A Perspective for Ménière’s Disease: In Silico Investigations of Dexamethasone as a Direct Modulator of AQP2 |
| title_full | A Perspective for Ménière’s Disease: In Silico Investigations of Dexamethasone as a Direct Modulator of AQP2 |
| title_fullStr | A Perspective for Ménière’s Disease: In Silico Investigations of Dexamethasone as a Direct Modulator of AQP2 |
| title_full_unstemmed | A Perspective for Ménière’s Disease: In Silico Investigations of Dexamethasone as a Direct Modulator of AQP2 |
| title_short | A Perspective for Ménière’s Disease: In Silico Investigations of Dexamethasone as a Direct Modulator of AQP2 |
| title_sort | perspective for meniere s disease in silico investigations of dexamethasone as a direct modulator of aqp2 |
| topic | human AQP2 dexamethasone Ménière’s disease water channel water permeability modulation molecular dynamics |
| url | https://www.mdpi.com/2218-273X/12/4/511 |
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