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dc.contributor.authorCastro-Sánchez, Saraes_ES
dc.contributor.authorZaldívar-Díez, Josefaes_ES
dc.contributor.authorLuengo, Enriquees_ES
dc.contributor.authorLópez, Manuela G.es_ES
dc.contributor.authorGil, Carmenes_ES
dc.contributor.authorMartínez Gil, Anaes_ES
dc.contributor.authorLastres-Becker, Isabeles_ES
dc.date.accessioned2020-10-09T08:55:58Z-
dc.date.available2020-10-09T08:55:58Z-
dc.date.issued2020-12-
dc.identifier.citationNeurobiology of Aging 96:148-154 (2020)es_ES
dc.identifier.issn0197-4580-
dc.identifier.urihttp://hdl.handle.net/10261/221008-
dc.description7 p.-2 fig.es_ES
dc.description.abstractLeucine-rich repeat kinase 2 (LRRK2) is a protein kinase whose activity plays an important role in neurodegenerative diseases. Although mutations in LRRK2 gene are the most common cause of monogenic Parkinson's disease, it has been reported that LRRK2 may promote Tau phosphorylation, increasing its aggregation. Thus, the modulation of LRRK2 activity by small molecules able to inhibit this kinase activity could be an innovative therapeutic strategy for different tauopathies. We examined the therapeutic effects of a new benzothiazole-based LRRK2 inhibitor, known as JZ1.40, in a mouse model of tauopathy. Mice were injected in the right hippocampus with an adeno-associated vector expressing human-TAUP301L and treated daily with JZ1.40 (10 mg/kg, i.p) or vehicle for three weeks. JZ1.40 reaches the brain and modulates RAB10 and Tau phosphorylation at the epitopes modified by LRRK2. Moreover, JZ1.40 treatment ameliorates the cognitive impairment induced by TAUP301L overexpression, which correlates with prevention of granular cell layer degeneration by improving synaptic plasticity. These data show that JZ1.40 is neuroprotective in vivo, which is translated into cognition enhancement.es_ES
dc.description.sponsorshipThis work was supported by MINECO (Competitiveness Grants SAF2016-76520-R to ILB, SAF2016-76693-R to AM, and RTI2018-095793-B-I00 to MGL), MECD (FPU grant FPU13-003262 to JZD), SCS is beneficiary of the call for predoctoral contracts for the training of research personnel 2018 (FPI-UAM) and Fundación Tatiana Pérez de Guzmán el Bueno to EL.es_ES
dc.language.isoenges_ES
dc.publisherElsevieres_ES
dc.relationSAF2016-76520-Res_ES
dc.relationSAF2016-76693-Res_ES
dc.relationRTI2018-095793-B-I00es_ES
dc.relation.isversionofPreprint-
dc.rightsopenAccesses_ES
dc.subjectTAUes_ES
dc.subjectPhospho-TAUes_ES
dc.subjectNeurodegenerationes_ES
dc.subjectSynaptic plasticityes_ES
dc.subjectTauopathyes_ES
dc.subjectLRRK2es_ES
dc.titleCognitive enhancement, TAU phosphorylation reduction, and neuronal protection by the treatment of an LRRK2 inhibitor in a tauopathy mouse modeles_ES
dc.typeartículoes_ES
dc.identifier.doi10.1016/j.neurobiolaging.2020.09.006-
dc.description.peerreviewedPeer reviewedes_ES
dc.relation.publisherversionhttps://doi.org/10.1016/j.neurobiolaging.2020.09.006es_ES
dc.contributor.funderMinisterio de Economía y Competitividad (España)es_ES
dc.contributor.funderMinisterio de Educación, Cultura y Deporte (España)es_ES
dc.contributor.funderMinisterio de Ciencia, Innovación y Universidades (España)es_ES
dc.contributor.funderUniversidad Autónoma de Madrides_ES
dc.contributor.funderFundación Tatiana Pérez de Guzmán el Buenoes_ES
dc.relation.csices_ES
oprm.item.hasRevisionno ko 0 false*
dc.identifier.funderhttp://dx.doi.org/10.13039/501100003176es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100004593es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100010805es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100003329es_ES
dc.contributor.orcidCastro-Sánchez, Sara [0000-0002-7175-9191]es_ES
dc.contributor.orcidZaldívar-Díez, Josefa [0000-0003-2317-3898]es_ES
dc.contributor.orcidLópez, Manuela G. [0000-0003-4461-8788]es_ES
dc.contributor.orcidGil, Carmen [0000-0002-3882-6081]es_ES
dc.contributor.orcidMartínez, Ana [0000-0002-2707-8110]es_ES
dc.contributor.orcidLastres-Becker,Isabel [0000-0002-4968-2175]es_ES
dc.type.coarhttp://purl.org/coar/resource_type/c_6501es_ES
item.openairetypeartículo-
item.cerifentitytypePublications-
item.languageiso639-1en-
item.grantfulltextopen-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.fulltextWith Fulltext-
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