Resveratrol protects against peripheral deficits in a mouse model of Huntington's disease.

Autor: Ho DJ; Weill Cornell Medical College, Department of Neurology and Neuroscience, 525 E. 68th Street, New York, NY 10065, USA., Calingasan NY, Wille E, Dumont M, Beal MF
Jazyk: angličtina
Zdroj: Experimental neurology [Exp Neurol] 2010 Sep; Vol. 225 (1), pp. 74-84. Date of Electronic Publication: 2010 Jun 01.
DOI: 10.1016/j.expneurol.2010.05.006
Abstrakt: Sirtuins are NAD-dependent deacetylases that regulate important biologic processes including transcription, cell survival and metabolism. Activation of SIRT1, a mammalian sirtuin, extends longevity and increases neuronal survival. An important substrate of SIRT1 is peroxisome proliferator-activated receptor gamma co-activator-1alpha (PGC-1alpha), a principal regulator of energy metabolism, whose function is significantly impaired in Huntington's disease (HD). We studied the effects of a pharmacological preparation of the SIRT1 activator resveratrol (SRT501-M), in the N171-82Q transgenic mouse model of HD. We analyzed motor performance, survival, central and peripheral pathology and levels of PGC-1alpha expression. Administration of SRT501-M increased expression of PGC-1alpha, as well as its downstream targets, nuclear respiratory factor-1 (NRF-1) and uncoupling protein-1 (UCP-1) in brown adipose tissue (BAT), but there was no effect on PGC-1alpha, NRF-1 or the mitochondrial transcription factor (Tfam) in the striatum. SRT501-M administration also reduced BAT vacuolation and decreased elevated blood glucose levels. However, there was no significant improvement in weight loss, motor performance, survival and striatal atrophy. Activation of the PGC-1alpha signaling pathway via resveratrol-induced activation of SIRT1, therefore, is an effective therapy in BAT, but not in the central nervous system of HD transgenic mice.
(Copyright 2010 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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