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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 
UID/NEU/ 04539/2013 
E-Rare4/0003/2012 Joint call for European Research Project on Rare Diseases 
French Muscular Dystrophy Association (AFM) 
National Ataxia Foundation (NAF) 
Richard Chin and Lily Lock Machado-Joseph disease Research Fund 
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.
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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