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http://hdl.handle.net/10261/221008
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Campo DC | Valor | Lengua/Idioma |
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dc.contributor.author | Castro-Sánchez, Sara | es_ES |
dc.contributor.author | Zaldívar-Díez, Josefa | es_ES |
dc.contributor.author | Luengo, Enrique | es_ES |
dc.contributor.author | López, Manuela G. | es_ES |
dc.contributor.author | Gil, Carmen | es_ES |
dc.contributor.author | Martínez Gil, Ana | es_ES |
dc.contributor.author | Lastres-Becker, Isabel | es_ES |
dc.date.accessioned | 2020-10-09T08:55:58Z | - |
dc.date.available | 2020-10-09T08:55:58Z | - |
dc.date.issued | 2020-12 | - |
dc.identifier.citation | Neurobiology of Aging 96:148-154 (2020) | es_ES |
dc.identifier.issn | 0197-4580 | - |
dc.identifier.uri | http://hdl.handle.net/10261/221008 | - |
dc.description | 7 p.-2 fig. | es_ES |
dc.description.abstract | Leucine-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.sponsorship | This 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.iso | eng | es_ES |
dc.publisher | Elsevier | es_ES |
dc.relation | SAF2016-76520-R | es_ES |
dc.relation | SAF2016-76693-R | es_ES |
dc.relation | RTI2018-095793-B-I00 | es_ES |
dc.relation.isversionof | Preprint | - |
dc.rights | openAccess | es_ES |
dc.subject | TAU | es_ES |
dc.subject | Phospho-TAU | es_ES |
dc.subject | Neurodegeneration | es_ES |
dc.subject | Synaptic plasticity | es_ES |
dc.subject | Tauopathy | es_ES |
dc.subject | LRRK2 | es_ES |
dc.title | Cognitive enhancement, TAU phosphorylation reduction, and neuronal protection by the treatment of an LRRK2 inhibitor in a tauopathy mouse model | es_ES |
dc.type | artículo | es_ES |
dc.identifier.doi | 10.1016/j.neurobiolaging.2020.09.006 | - |
dc.description.peerreviewed | Peer reviewed | es_ES |
dc.relation.publisherversion | https://doi.org/10.1016/j.neurobiolaging.2020.09.006 | es_ES |
dc.contributor.funder | Ministerio de Economía y Competitividad (España) | es_ES |
dc.contributor.funder | Ministerio de Educación, Cultura y Deporte (España) | es_ES |
dc.contributor.funder | Ministerio de Ciencia, Innovación y Universidades (España) | es_ES |
dc.contributor.funder | Universidad Autónoma de Madrid | es_ES |
dc.contributor.funder | Fundación Tatiana Pérez de Guzmán el Bueno | es_ES |
dc.relation.csic | Sí | es_ES |
oprm.item.hasRevision | no ko 0 false | * |
dc.identifier.funder | http://dx.doi.org/10.13039/501100003176 | es_ES |
dc.identifier.funder | http://dx.doi.org/10.13039/501100004593 | es_ES |
dc.identifier.funder | http://dx.doi.org/10.13039/501100010805 | es_ES |
dc.identifier.funder | http://dx.doi.org/10.13039/501100003329 | es_ES |
dc.contributor.orcid | Castro-Sánchez, Sara [0000-0002-7175-9191] | es_ES |
dc.contributor.orcid | Zaldívar-Díez, Josefa [0000-0003-2317-3898] | es_ES |
dc.contributor.orcid | López, Manuela G. [0000-0003-4461-8788] | es_ES |
dc.contributor.orcid | Gil, Carmen [0000-0002-3882-6081] | es_ES |
dc.contributor.orcid | Martínez, Ana [0000-0002-2707-8110] | es_ES |
dc.contributor.orcid | Lastres-Becker,Isabel [0000-0002-4968-2175] | es_ES |
dc.type.coar | http://purl.org/coar/resource_type/c_6501 | es_ES |
item.openairetype | artículo | - |
item.cerifentitytype | Publications | - |
item.languageiso639-1 | en | - |
item.grantfulltext | open | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.fulltext | With Fulltext | - |
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Cognitive_Isabel_Preprint_2020.pdf | 354,08 kB | Adobe PDF | Visualizar/Abrir |
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