English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/139352
Share/Impact:
Statistics
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:
DC FieldValueLanguage
dc.contributor.authorTrovó, Laura-
dc.contributor.authorStroobants, Stijn-
dc.contributor.authorD'Hooge, Rudi-
dc.contributor.authorLedesma, M. Dolores-
dc.contributor.authorDotti, Carlos G.-
dc.date.accessioned2016-10-26T08:07:12Z-
dc.date.available2016-10-26T08:07:12Z-
dc.date.issued2015-
dc.identifierdoi: 10.1016/j.nbd.2014.09.008-
dc.identifierissn: 1095-953X-
dc.identifier.citationNeurobiology of Disease 73: 319- 326 (2015)-
dc.identifier.urihttp://hdl.handle.net/10261/139352-
dc.description.abstract© 2014 Elsevier Inc. Niemann-Pick disease type A (NPDA) is a fatal disease due to mutations in the acid sphingomyelinase (ASM) gene, which triggers the abnormal accumulation of sphingomyelin (SM) in lysosomes and the plasma membrane of mutant cells. Although the disease affects multiple organs, the impact on the brain is the most invalidating feature. The mechanisms responsible for the cognitive deficit characteristic of this condition are only partially understood. Using mice lacking the ASM gene (ASMko), a model system in NPDA research, we report here that high sphingomyelin levels in mutant neurons lead to low synaptic levels of phosphoinositide PI(4,5)P2 and reduced activity of its hydrolyzing phosphatase PLCγ, which are key players in synaptic plasticity events. In addition, mutant neurons have reduced levels of membrane-bound MARCKS, a protein required for PI(4,5)P2 membrane clustering and hydrolysis. Intracerebroventricular infusion of a peptide that mimics the effector domain of MARCKS increases the content of PI(4,5)P2 in the synaptic membrane and ameliorates behavioral abnormalities in ASMko mice.-
dc.description.sponsorshipFund for Scientific Research Flanders (FWO) G0.666.10N (CGD) and G0D7614N (RD'H), Interuniversity Attraction Poles Program IUAP P6P7/1658 (RD'H) and Neurobrainnet IAP 7/16 (CGD) of the Belgian Federal Science Policy Office and Methusalem grant of the Flemish Government, Spanish Ministry of Science and Innovation Ingenio-Consolider CSD2010-00064 and SAF2010-14906 and Spanish Ministry of Economy and Competitiveness SAF2013-45392 to CGD-
dc.publisherAcademic Press-
dc.rightsopenAccess-
dc.subjectPI(4,5)P2-
dc.subjectASMko mice-
dc.subjectBehavior-
dc.subjectMARCKS-
dc.titleImprovement of biochemical and behavioral defects in the Niemann-Pick type A mouse by intraventricular infusion of MARCKS-
dc.typeartículo-
dc.identifier.doi10.1016/j.nbd.2014.09.008-
dc.date.updated2016-10-26T08:07:13Z-
dc.description.versionPeer Reviewed-
dc.language.rfc3066eng-
dc.contributor.funderMinisterio de Economía y Competitividad (España)-
dc.contributor.funderMinisterio de Ciencia e Innovación (España)-
dc.contributor.funderNational Fund for Scientific Research (Belgium)-
dc.identifier.funderhttp://dx.doi.org/10.13039/501100003329es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100004837es_ES
Appears in Collections:(CBM) Artículos
Files in This Item:
File Description SizeFormat 
524874.png115,22 kBUnknownView/Open
Show simple item record
 

Related articles:


WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.