Por favor, use este identificador para citar o enlazar a este item:
http://hdl.handle.net/10261/189019
COMPARTIR / EXPORTAR:
SHARE CORE BASE | |
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE | |
Título: | Targeting the neuronal calcium sensor DREAM with small-molecules for Huntington’s disease treatment |
Autor: | López-Hurtado, Alejandro; Peraza, Diego A. CSIC ORCID; Cercós, Pilar CSIC; Lagartera, Laura CSIC ORCID; González Pérez, Paz; Dopazo, Xose M.; Herranz, Rosario CSIC ORCID; González, Teresa CSIC ORCID; Martín-Martínez, Mercedes CSIC ORCID; Mellström, Britt CSIC; Naranjo, José Ramón CSIC ORCID; Valenzuela, Carmen CSIC ORCID CVN; Gutiérrez-Rodríguez, Marta CSIC ORCID | Fecha de publicación: | 2019 | Editor: | Springer Nature | Citación: | Scientific Reports 9: 7260 (2019) | Resumen: | DREAM, a neuronal calcium sensor protein, has multiple cellular roles including the regulation of Ca2+ and protein homeostasis. We recently showed that reduced DREAM expression or blockade of DREAM activity by repaglinide is neuroprotective in Huntington's disease (HD). Here we used structure-based drug design to guide the identification of IQM-PC330, which was more potent and had longer lasting effects than repaglinide to inhibit DREAM in cellular and in vivo HD models. We disclosed and validated an unexplored ligand binding site, showing Tyr118 and Tyr130 as critical residues for binding and modulation of DREAM activity. IQM-PC330 binding de-repressed c-fos gene expression, silenced the DREAM effect on KV4.3 channel gating and blocked the ATF6/DREAM interaction. Our results validate DREAM as a valuable target and propose more effective molecules for HD treatment. | Versión del editor: | https://doi.org/10.1038/s41598-019-43677-7 | URI: | http://hdl.handle.net/10261/189019 | DOI: | 10.1038/s41598-019-43677-7 | E-ISSN: | 2045-2322 |
Aparece en las colecciones: | (IIBM) Artículos (IQM) Artículos (CNB) Artículos |
Ficheros en este ítem:
Fichero | Descripción | Tamaño | Formato | |
---|---|---|---|---|
targetdise.pdf | 3,89 MB | Adobe PDF | Visualizar/Abrir |
CORE Recommender
PubMed Central
Citations
8
checked on 20-abr-2024
SCOPUSTM
Citations
11
checked on 23-abr-2024
WEB OF SCIENCETM
Citations
11
checked on 25-feb-2024
Page view(s)
188
checked on 26-abr-2024
Download(s)
127
checked on 26-abr-2024