کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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3056056 | 1186552 | 2010 | 11 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Resveratrol protects against peripheral deficits in a mouse model of Huntington's disease Resveratrol protects against peripheral deficits in a mouse model of Huntington's disease](/preview/png/3056056.png)
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-1α (PGC-1α), 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-1α expression. Administration of SRT501-M increased expression of PGC-1α, 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-1α, 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-1α 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.
Journal: Experimental Neurology - Volume 225, Issue 1, September 2010, Pages 74–84