Caloric restriction blocks neuropathology and motor deficits in Machado–Joseph disease mouse models through SIRT1 pathway

Janete Cunha-Santos, Joana Duarte-Neves, Vitor Carmona, Leonard Guarente, Luís Pereira de Almeida () and Cláudia Cavadas ()
Additional contact information
Janete Cunha-Santos: CNC—Center for Neuroscience and Cell Biology, University of Coimbra, Rua Larga
Joana Duarte-Neves: CNC—Center for Neuroscience and Cell Biology, University of Coimbra, Rua Larga
Vitor Carmona: CNC—Center for Neuroscience and Cell Biology, University of Coimbra, Rua Larga
Leonard Guarente: Massachusetts Institute of Technology
Luís Pereira de Almeida: CNC—Center for Neuroscience and Cell Biology, University of Coimbra, Rua Larga
Cláudia Cavadas: CNC—Center for Neuroscience and Cell Biology, University of Coimbra, Rua Larga

Nature Communications, 2016, vol. 7, issue 1, 1-14

Abstract: 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.

Date: 2016
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms11445 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11445

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms11445

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().