The synthetic progestin norgestrel modulates Nrf2 signaling and acts as an antioxidant in a model of retinal degeneration

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dc.contributor.authorByrne, Ashleigh M.
dc.contributor.authorRuiz-Lopez, Ana M.
dc.contributor.authorRoche, Sarah L.
dc.contributor.authorMoloney, Jennifer N.
dc.contributor.authorWyse-Jackson, Alice C.
dc.contributor.authorCotter, Thomas G.
dc.contributor.funderScience Foundation Irelanden
dc.contributor.funderFighting Blindness Irelanden
dc.date.accessioned2016-10-28T14:37:51Z
dc.date.available2016-10-28T14:37:51Z
dc.date.issued2016-10-04
dc.description.abstractRetinitis pigmentosa (RP) is one of the most common retinal degenerative conditions affecting people worldwide, and is currently incurable. It is characterized by the progressive loss of photoreceptors, in which the death of rod cells leads to the secondary death of cone cells; the cause of eventual blindness. As rod cells die, retinal-oxygen metabolism becomes perturbed, leading to increased levels of reactive oxygen species (ROS) and thus oxidative stress; a key factor in the secondary death of cones. In this study, norgestrel, an FDA-approved synthetic analog of progesterone, was found to be a powerful neuroprotective antioxidant, preventing light-induced ROS in photoreceptor cells, and subsequent cell death. Norgestrel also prevented light-induced photoreceptor morphological changes that were associated with ROS production, and that are characteristic of RP. Further investigation showed that norgestrel acts via post-translational modulation of the major antioxidant transcription factor Nrf2; bringing about its phosphorylation, subsequent nuclear translocation, and increased levels of its effector protein superoxide dismutase 2 (SOD2). In summary, these results demonstrate significant protection of photoreceptor cells from oxidative stress, and underscore the potential of norgestrel as a therapeutic option for RP.en
dc.description.sponsorshipScience Foundation Ireland (SFI grant no. 13/IA/1783)en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationByrne, A. M., Ruiz-Lopez, A. M., Roche, S. L., Moloney, J. N., Wyse -Jackson, A. C. & Cotter, T. G. (2016) ‘The synthetic progestin norgestrel modulates Nrf2 signaling and acts as an antioxidant in a model of retinal degeneration’, Redox Biology, 10, 128-139. doi: 10.1016/j.redox.2016.10.002en
dc.identifier.doi10.1016/j.redox.2016.10.002
dc.identifier.endpage139en
dc.identifier.issn2213-2317
dc.identifier.journaltitleRedox Biologyen
dc.identifier.startpage128en
dc.identifier.urihttps://hdl.handle.net/10468/3227
dc.identifier.volume10en
dc.language.isoenen
dc.publisherElsevieren
dc.rights© 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by/4.0/).en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectRetinitis pigmentosaen
dc.subjectPhotoreceptorsen
dc.subjectROSen
dc.subjectNrf2en
dc.subjectNorgestrelen
dc.subjectRetinal degenerationen
dc.subjectBlindnessen
dc.titleThe synthetic progestin norgestrel modulates Nrf2 signaling and acts as an antioxidant in a model of retinal degenerationen
dc.typeArticle (peer-reviewed)en
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