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dc.contributor.authorZaldívar-Díez, Josefaes_ES
dc.contributor.authorLi, Linglinges_ES
dc.contributor.authorGarcía, Ana M.es_ES
dc.contributor.authorZhao, Wenninges_ES
dc.contributor.authorMedina-Menendez, Cristinaes_ES
dc.contributor.authorHaggarty, Stephen J.es_ES
dc.contributor.authorGil, Carmenes_ES
dc.contributor.authorMorales, Aixa V.es_ES
dc.contributor.authorMartínez, Anaes_ES
dc.date.accessioned2019-12-19T14:12:19Z-
dc.date.available2019-12-19T14:12:19Z-
dc.date.issued2019-12-11-
dc.identifier.citationJournal of Medicinal Chemistry 63 (5) 2638-2655 (2020)-
dc.identifier.issn0022-2623-
dc.identifier.urihttp://hdl.handle.net/10261/197077-
dc.description63 p.-15 fig.-1 tab.-2 schem.es_ES
dc.description.abstractLeucine Rich Repeat Kinase 2 (LRRK2) is an enigmatic enzyme and a relevant target for Parkinson’s Disease (PD). However, despite the significant amount of research done in the last decade, the precise function of LRRK2 remains largely unknown. Moreover, the therapeutic potential of its inhibitors is in its infancy with the first clinical trial having just started. In the present work the molecular mechanism of LRRK2 in the control of neurogenesis or gliogenesis was investigated. We designed and synthesized novel benzothiazole-based LRRK2 inhibitors and showed that they can modulate the Wnt/β-catenin signaling pathway. Furthermore, compounds 5 and 14 were able to promote neural progenitors proliferation and drive their differentiation towards neuronal and oligodendrocytic cell fates. These results suggest potential new avenues for the application of LRRK2 inhibitors in demyelinating diseases in which oligodendrocyte cell-death is one of the pathological features.es_ES
dc.description.sponsorshipThis work was supported by MINECO (grant SAF2016-76693-R to A.M. and SAF2017-85717-R to A.V.M.), CIBERNED (CB18/05/00040 to A.M.), MECD (FPU13-003262 to J.Z.-D.), CEU-Banco Santander (Scholarships for the Research Mobility Program CEU-BANCO SANTANDER to J.Z.-D.), Fundación Alicia Koplowitz (Research Project, 2018 to A.V.M.) and Tau Consortium and Stuart & Suzanne Steele MGH Research Scholar Award to S.J.Hes_ES
dc.language.isoenges_ES
dc.publisherAmerican Chemical Societyes_ES
dc.relationMINECO/ICTI2013-2016/SAF2016-76693-Res_ES
dc.relationMICIU/ICTI2017-2021/SAF2017-85717-Res_ES
dc.relation.isversionofPostprintes_ES
dc.rightsopenAccesses_ES
dc.subjectLRRK2 inhibitorses_ES
dc.subjectAdult neurogenesises_ES
dc.subjectWnt enhancerses_ES
dc.subjectOligodendrocyte differentiationes_ES
dc.titleBenzothiazole-based LRRK2 inhibitors as Wnt enhancers and promoters of oligodendrocytic fatees_ES
dc.typeartículoes_ES
dc.identifier.doihttp://dx.doi.org/10.1021/acs.jmedchem.9b01752-
dc.description.peerreviewedPeer reviewedes_ES
dc.relation.publisherversionhttps://doi.org/10.1021/acs.jmedchem.9b01752es_ES
dc.identifier.e-issn1520-4804-
dc.embargo.terms2020-12-11es_ES
dc.contributor.funderMinisterio de Economía y Competitividad (España)es_ES
dc.contributor.funderBanco Santanderes_ES
dc.contributor.funderFundación Alicia Koplowitzes_ES
dc.relation.csices_ES
oprm.item.hasRevisionno ko 0 false*
dc.identifier.funderhttp://dx.doi.org/10.13039/100008062es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/100010784es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100003329es_ES
dc.contributor.orcidHaggarty, Stephen J. [0000-0002-7872-168X]es_ES
dc.contributor.orcidGil, Carmen [0000-0002-3882-6081]es_ES
dc.contributor.orcidMorales, Aixa V. [0000-0001-6295-5142]es_ES
dc.contributor.orcidMartínez, Ana [0000-0002-2707-8110]es_ES
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