Nrf2: a novel therapeutic target in fragile X syndrome is modulated by NNZ2566
Author | dc.contributor.author | Deacon, R. M. J. | |
Author | dc.contributor.author | Hurley, M. J. | |
Author | dc.contributor.author | Rebolledo, C. M. | |
Author | dc.contributor.author | Snape, M. | |
Author | dc.contributor.author | Altimiras, F. J. | |
Author | dc.contributor.author | Farias, L. | |
Author | dc.contributor.author | Pino, M. | |
Author | dc.contributor.author | Biekofsky, R. | |
Author | dc.contributor.author | Glass, L. | |
Author | dc.contributor.author | Cogram, Patricia | |
Admission date | dc.date.accessioned | 2018-07-13T14:06:22Z | |
Available date | dc.date.available | 2018-07-13T14:06:22Z | |
Publication date | dc.date.issued | 2017 | |
Cita de ítem | dc.identifier.citation | Genes Brain and Behavior 16 (7) : 1-10 | es_ES |
Identifier | dc.identifier.other | 10.1111/gbb.12373 | |
Identifier | dc.identifier.uri | https://repositorio.uchile.cl/handle/2250/149843 | |
Abstract | dc.description.abstract | Fragile X-associated disorders are a family of genetic conditions resulting from the partial or complete loss of fragile X mental retardation protein (FMRP). Among these disorders, fragile X syndrome (FXS) is the most common cause of inherited intellectual disability and autism. Progress in basic neuroscience has led to identification of molecular targets for treatment in FXS; however, there is a gap in translation to targeted therapies in humans. This study introduces a novel therapeutic target for FXS, nuclear factor (erythroid-derived 2)-like 2 (Nrf2), a transcription factor known to induce expression of over 100 cytoprotective genes. We also show that NNZ2566, a drug that has successfully completed a phase 2 clinical trial in FXS, is effective in modulating this target in FXS, partially reversing the FXS phenotype; NNZ2566 has a therapeutic role as Nrf2 activator. Effectively, treatment with NNZ2566 normalizes the translocation of Nrf2 to the nucleus, inducing expression of numerous oxidative stress-related genes including NQO1 (NAD(P) H dehydrogenase quinone 1), GST-alpha 1 (glutathione S-transferase alpha-1) and EH (epoxide hydrolase) and has a knockdown effect on E-cadherin. In summary, the Nrf2/ARE (antioxidant response element) pathway appears to be a novel promising therapeutic target for FXS and NNZ2566 appears to be acting as an activator of the Nrf2/ARE pathway and suggests a potential benefit across multiple symptoms that could be associated with the pathobiological processes underlying FXS. | es_ES |
Patrocinador | dc.description.sponsorship | FRAXA Research Foundation Neuren Pharmaceuticals Ltd NNZ2566 | es_ES |
Lenguage | dc.language.iso | en | es_ES |
Publisher | dc.publisher | Wiley | es_ES |
Source | dc.source | Genes Brain and Behavior | es_ES |
Keywords | dc.subject | Autism spectrum disorder | es_ES |
Keywords | dc.subject | Behavior | es_ES |
Keywords | dc.subject | E-cadherin | es_ES |
Keywords | dc.subject | Fmr1 knockout mouse | es_ES |
Keywords | dc.subject | Fragile X syndrome | es_ES |
Keywords | dc.subject | GST-alpha 1 | es_ES |
Keywords | dc.subject | NNZ2566 | es_ES |
Keywords | dc.subject | NQO1 | es_ES |
Keywords | dc.subject | Nrf2/ARE pathway | es_ES |
Keywords | dc.subject | Oxidative stress | es_ES |
Título | dc.title | Nrf2: a novel therapeutic target in fragile X syndrome is modulated by NNZ2566 | es_ES |
Document type | dc.type | Artículo de revista | |
dcterms.accessRights | dcterms.accessRights | Acceso a solo metadatos | es_ES |
Cataloguer | uchile.catalogador | tjn | es_ES |
Indexation | uchile.index | Artículo de publicación ISI | es_ES |
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