2. Academic Validation
  3. Sirtuin 1 activator SRT2104 protects Huntington's disease mice

Sirtuin 1 activator SRT2104 protects Huntington's disease mice

  • Ann Clin Transl Neurol. 2014 Dec;1(12):1047-52. doi: 10.1002/acn3.135.
Mali Jiang 1,  Jennifer Zheng 1,  Qi Peng 1,  Zhipeng Hou 2,  Jiangyang Zhang 2,  Susumu Mori 2,  James L Ellis 3,  George P Vlasuk 3,  Harvey Fries 3,  Vipin Suri 3,  Wenzhen Duan 4
Affiliations

Affiliations

  • 1 Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, School of Medicine, Johns Hopkins University Baltimore, Maryland, 21287.
  • 2 Department of Radiology, School of Medicine, Johns Hopkins University Baltimore, Maryland, 21287.
  • 3 Sirtris, a GSK company Collegeville, Pennsylvania, 19426.
  • 4 Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, School of Medicine, Johns Hopkins University Baltimore, Maryland, 21287 ; Department of Neuroscience, School of Medicine, Johns Hopkins University Baltimore, Maryland, 21287 ; Program in Cellular and Molecular Medicine, School of Medicine, Johns Hopkins University Baltimore, Maryland, 21287.
PMID: 25574479 DOI: 10.1002/acn3.135
Abstract

Sirtuin 1 is a nicotinamide adenine dinucleotide-dependent protein deacetylase which regulates longevity and improves metabolism. Activation of Sirtuin 1 confers beneficial effects in models of neurodegenerative diseases. We and Others have provided convincing evidence that overexpression of Sirtuin 1 plays a neuroprotective role in mouse models of Huntington's disease. In this study, we report that SRT2104, a small molecule Sirtuin 1 activator, penetrated the blood-brain barrier, attenuated brain atrophy, improved motor function, and extended survival in a mouse model of Huntington's disease. These findings imply a novel therapeutic strategy for Huntington's disease by targeting Sirtuin 1.

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