Utilize este identificador para referenciar este registo:
https://hdl.handle.net/1822/57781
Registo completo
Campo DC | Valor | Idioma |
---|---|---|
dc.contributor.author | Ashraf, Naila S. | por |
dc.contributor.author | Silva, Sara Carina Duarte | por |
dc.contributor.author | Shaw, Emily D. | por |
dc.contributor.author | Maciel, P. | por |
dc.contributor.author | Paulson, Henry L. | por |
dc.contributor.author | Castro, Andreia Cristiana Teixeira | por |
dc.contributor.author | Costa, Maria do Carmo | por |
dc.date.accessioned | 2019-01-04T09:33:26Z | - |
dc.date.available | 2019-09-04T06:00:12Z | - |
dc.date.issued | 2019 | - |
dc.identifier.issn | 0893-7648 | por |
dc.identifier.uri | https://hdl.handle.net/1822/57781 | - |
dc.description.abstract | Machado-Joseph disease, also known as spinocerebellar ataxia type 3, is a fatal polyglutamine disease with no disease-modifying treatment. The selective serotonin reuptake inhibitor citalopram was shown in nematode and mouse models to be a compelling repurposing candidate for Machado-Joseph disease therapeutics. We sought to confirm the efficacy of citalopram to decrease ATXN3 aggregation in an unrelated mouse model of Machado-Joseph disease. Four-week-old YACMJD84.2 mice and non-transgenic littermates were given citalopram 8 mg/kg in drinking water or water for 10 weeks. At the end of treatment, brains were collected for biochemical and pathological analyses. Brains of citalopram-treated YACMJD84.2 mice showed an approximate 50% decrease in the percentage of cells containing ATXN3-positive inclusions in the substantia nigra and three examined brainstem nuclei compared to controls. No differences in ATXN3 inclusion load were observed in deep cerebellar nuclei of mice. Citalopram effect on ATXN3 aggregate burden was corroborated by immunoblotting analysis. While lysates from the brainstem and cervical spinal cord of citalopram-treated mice showed a decrease in all soluble forms of ATXN3 and a trend toward reduction of insoluble ATXN3, no differences in ATXN3 levels were found between cerebella of citalopram-treated and vehicle-treated mice. Citalopram treatment altered levels of select components of the cellular protein homeostatic machinery that may be expected to enhance the capacity to refold and/or degrade mutant ATXN3. The results here obtained in a second independent mouse model of Machado-Joseph disease further support citalopram as a potential drug to be repurposed for this fatal disorder. | por |
dc.description.sponsorship | This work was funded by Becky Babcox Research Fund/pilot research award G015617, University of Michigan to M.C.C. and NINDS/NIH R01NS038712 to H.L.P. The work performed at the University of Minho was funded by the European Regional Development Funds (FEDER), through the Competitiveness Factors Operational Programme (COMPETE), and by National funds, through the Foundation for Science and Technology (FCT), under the scope of the project POCI-01-0145-FEDER-007038. This article was developed under the scope of the project NORTE-01-0145-FEDER-000013, supported by the Northern Portugal Regional Operational Program (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the FEDER. This work was also supported by FCT and COMPETE through the projects [PTDC/SAU-GMG/112617/2009] (to P.M.) and [EXPL/BIM-MEC/ 0239/2012] (to A.T.C.); by FCT through the project [POCI-01-0145- FEDER-016818 (PTDC/NEU-NMC/3648/2014)] (to P.M.); by National Ataxia Foundation (to P.M. and to A.T.C.); and by Ataxia UK (to P.M.). S.D.S. and A.T.C. were supported by fellowships from FCT, SFRH/BD/ 78388/2011 and SFRH/BPD/102317/2014, respectively. FCT fellowships are co-financed by POPH, QREN, Governo da República Portuguesa and EU/FSE. | por |
dc.language.iso | eng | por |
dc.publisher | Springer | - |
dc.relation | info:eu-repo/grantAgreement/FCT/5876-PPCDTI/PTDC%2FSAU-GMG%2F112617%2F2009/PT | - |
dc.relation | info:eu-repo/grantAgreement/FCT/5876-PPCDTI/EXPL%2FBIM-MEC%2F0239%2F2012/PT | - |
dc.relation | info:eu-repo/grantAgreement/FCT/9471 - RIDTI/PTDC%2FNEU-NMC%2F3648%2F2014/PT | - |
dc.relation | info:eu-repo/grantAgreement/FCT/FARH/SFRH%2FBD%2F78388%2F2011/PT | - |
dc.relation | info:eu-repo/grantAgreement/FCT/OE/SFRH%2FBPD%2F102317%2F2014/PT | - |
dc.rights | openAccess | por |
dc.subject | Neurodegeneration | por |
dc.subject | Polyglutamine | por |
dc.subject | Proteinopathy | por |
dc.subject | Spinocerebellar ataxia | por |
dc.subject | Therapy | por |
dc.title | Citalopram reduces aggregation of ATXN3 in a YAC transgenic mouse model of Machado-Joseph disease | por |
dc.type | article | por |
dc.peerreviewed | yes | por |
oaire.citationStartPage | 3690 | por |
oaire.citationEndPage | 3701 | por |
oaire.citationIssue | 5 | por |
oaire.citationVolume | 56 | por |
dc.identifier.doi | 10.1007/s12035-018-1331-2 | por |
dc.identifier.pmid | 30187384 | por |
dc.subject.wos | Science & Technology | por |
sdum.journal | Molecular Neurobiology | por |
Aparece nas coleções: | ICVS - Artigos em revistas internacionais / Papers in international journals |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
---|---|---|---|---|
Ashraf2018_Article_CitalopramReducesAggregationOf.pdf | 8,67 MB | Adobe PDF | Ver/Abrir |