Linked Life Data

20668093

Source:http://linkedlifedata.com/resource/pubmed/id/20668093

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
20
pubmed:dateCreated
2010-9-30
pubmed:abstractText
Huntington's disease (HD) is a neurodegenerative disease caused by the expansion of a CAG trinucleotide repeat in exon 1 of the huntingtin (HTT) gene. Here, we report that the transcript of the peroxisome proliferator-activated receptor-? (PPAR?), a transcription factor that is critical for energy homeostasis, was markedly downregulated in multiple tissues of a mouse model (R6/2) of HD and in lymphocytes of HD patients. Therefore, downregulation of PPAR? seems to be a pathomechanism of HD. Chronic treatment of R6/2 mice with an agonist of PPAR? (thiazolidinedione, TZD) rescued progressive weight loss, motor deterioration, formation of mutant Htt aggregates, jeopardized global ubiquitination profiles, reduced expression of two neuroprotective proteins (brain-derived neurotrophic factor and Bcl-2) and shortened life span exhibited by these mice. By reducing HTT aggregates and, thus, ameliorating the recruitment of PPAR? into HTT aggregates, chronic TZD treatment also elevated the availability of the PPAR? protein and subsequently normalized the expression of two of its downstream genes (the glucose transporter type 4 and PPAR? coactivator-1 alpha genes). The protective effects described above appear to have been exerted, at least partially, via direct activation of PPAR? in the brain, as TZD was detected in the brains of mice treated with TZD and because a PPAR? agonist (rosiglitazone) protected striatal cells from mHTT-evoked energy deficiency and toxicity. We demonstrated that the systematic downregulation of PPAR? seems to play a critical role in the dysregulation of energy homeostasis observed in HD, and that PPAR? is a potential therapeutic target for this disease.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1460-2083
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
19
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4043-58
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Modulation of energy deficiency in Huntington's disease via activation of the peroxisome proliferator-activated receptor gamma.
pubmed:affiliation
Institute of Biomedical Sciences, Academia Sinica, Nankang, Taipei 115, Taiwan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't