Caloric restriction blocks neuropathology and motor deficits in Machado–Joseph disease mouse models through SIRT1 pathway
Name
Caloric Restriction Blocks.pdf
Size
2.4 MB
Format
Adobe PDF
Checksum (MD5)
1a13118d5d13f7022202cda1c2cb2a50
Author(s)
Cunha-Santos, Janete
Duarte-Neves, Joana
Carmona, Vitor
Pereira de Almeida, Luís
Cavadas, Cláudia
Guarente, Leonard Pershing
Date Issued
May 2016
Journal
Nature Communications
Publisher
Nature Publishing Group
Citation
Cunha-Santos, Janete et al. “Caloric Restriction Blocks Neuropathology and Motor Deficits in Machado–Joseph Disease Mouse Models through SIRT1 Pathway.” Nature Communications 7 (2016): 11445. © 2017 Macmillan Publishers Limited
Version
Final published version
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Paul F. Glenn Center for Biology of Aging Research (Massachusetts Institute of Technology)
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution 4.0 International License
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1038/ncomms11445
