PMID- 20561979
OWN - NLM
STAT- MEDLINE
DCOM- 20101020
LR  - 20211020
IS  - 1090-2430 (Electronic)
IS  - 0014-4886 (Linking)
VI  - 225
IP  - 1
DP  - 2010 Sep
TI  - Resveratrol protects against peripheral deficits in a mouse model of Huntington's 
      disease.
PG  - 74-84
LID - 10.1016/j.expneurol.2010.05.006 [doi]
AB  - 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.
CI  - Copyright 2010 Elsevier Inc. All rights reserved.
FAU - Ho, Daniel J
AU  - Ho DJ
AD  - Weill Cornell Medical College, Department of Neurology and Neuroscience, 525 E. 
      68th Street, New York, NY 10065, USA.
FAU - Calingasan, Noel Y
AU  - Calingasan NY
FAU - Wille, Elizabeth
AU  - Wille E
FAU - Dumont, Magali
AU  - Dumont M
FAU - Beal, M Flint
AU  - Beal MF
LA  - eng
GR  - R01 NS039258/NS/NINDS NIH HHS/United States
GR  - NS39258/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20100601
PL  - United States
TA  - Exp Neurol
JT  - Experimental neurology
JID - 0370712
RN  - 0 (Antioxidants)
RN  - 0 (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha)
RN  - 0 (Ppargc1a protein, mouse)
RN  - 0 (Stilbenes)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - EC 3.5.1.- (Sirt1 protein, mouse)
RN  - EC 3.5.1.- (Sirtuin 1)
RN  - Q369O8926L (Resveratrol)
SB  - IM
CIN - Exp Neurol. 2011 Nov;232(1):1-6. PMID: 21907197
MH  - Adipose Tissue, Brown/drug effects/metabolism
MH  - Animals
MH  - Antioxidants/pharmacology/therapeutic use
MH  - *Disease Models, Animal
MH  - Down-Regulation/drug effects/genetics
MH  - Huntington Disease/*drug therapy/genetics/*metabolism
MH  - Mice
MH  - Mice, Inbred C3H
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
MH  - Resveratrol
MH  - Sirtuin 1/biosynthesis/deficiency/physiology
MH  - Stilbenes/*pharmacology/*therapeutic use
MH  - Trans-Activators/biosynthesis/deficiency/physiology
MH  - Transcription Factors
MH  - Treatment Outcome
EDAT- 2010/06/22 06:00
MHDA- 2010/10/21 06:00
CRDT- 2010/06/22 06:00
PHST- 2010/02/24 00:00 [received]
PHST- 2010/04/20 00:00 [revised]
PHST- 2010/05/12 00:00 [accepted]
PHST- 2010/06/22 06:00 [entrez]
PHST- 2010/06/22 06:00 [pubmed]
PHST- 2010/10/21 06:00 [medline]
AID - S0014-4886(10)00164-0 [pii]
AID - 10.1016/j.expneurol.2010.05.006 [doi]
PST - ppublish
SO  - Exp Neurol. 2010 Sep;225(1):74-84. doi: 10.1016/j.expneurol.2010.05.006. Epub 
      2010 Jun 1.