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Title: | Caloric restriction blocks neuropathology and motor deficits in Machado-Joseph disease mouse models through SIRT1 pathway | Authors: | Cunha-Santos, Janete Duarte-Neves, Joana Carmona, Vitor Guarente, Leonard Almeida, Luís Pereira de Cavadas, Cláudia |
Issue Date: | 11-May-2016 | Publisher: | Springer Nature | Project: | CENTRO-07-ST24-FEDER-002002 SFRH/BD/87404/2012 SFRH/BD/74993/2010 SRFH/BD/87048/2012 info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID/NEU/04539/2013/PT E-Rare4/0003/2012 |
Serial title, monograph or event: | Nature Communications | Volume: | 7 | Issue: | 1 | Abstract: | Machado-Joseph disease (MJD) is a neurodegenerative disorder characterized by an abnormal expansion of the CAG triplet in the ATXN3 gene, translating into a polyglutamine tract within the ataxin-3 protein. The available treatments only ameliorate symptomatology and do not block disease progression. In this study we find that caloric restriction dramatically rescues the motor incoordination, imbalance and the associated neuropathology in transgenic MJD mice. We further show that caloric restriction rescues SIRT1 levels in transgenic MJD mice, whereas silencing SIRT1 is sufficient to prevent the beneficial effects on MJD pathology. In addition, the re-establishment of SIRT1 levels in MJD mouse model, through the gene delivery approach, significantly ameliorates neuropathology, reducing neuroinflammation and activating autophagy. Furthermore, the pharmacological activation of SIRT1 with resveratrol significantly reduces motor incoordination of MJD mice. The pharmacological SIRT1 activation could provide important benefits to treat MJD patients. | URI: | https://hdl.handle.net/10316/108721 | ISSN: | 2041-1723 | DOI: | 10.1038/ncomms11445 | Rights: | openAccess |
Appears in Collections: | FFUC- Artigos em Revistas Internacionais I&D CNC - Artigos em Revistas Internacionais |
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Caloric restriction blocks neuropathology and motor deficits in Machado-Joseph disease mouse models through SIRT1 pathway.pdf | 2.07 MB | Adobe PDF | View/Open |
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