当前位置： SCI文献检索 > BIOCHEMICAL SOCIETY TRANSACTIONS期刊下所有文献 > Transcriptional dysregulation of coding and non-coding genes in cellular models of Huntington's disease.

Transcriptional dysregulation of coding and non-coding genes in cellular models of Huntington's disease.

Abstract：

:HD (Huntington's disease) is a late onset heritable neurodegenerative disorder that is characterized by neuronal dysfunction and death, particularly in the cerebral cortex and medium spiny neurons of the striatum. This is followed by progressive chorea, dementia and emotional dysfunction, eventually resulting in death. HD is caused by an expanded CAG repeat in the first exon of the HD gene that results in an abnormally elongated polyQ (polyglutamine) tract in its protein product, Htt (Huntingtin). Wild-type Htt is largely cytoplasmic; however, in HD, proteolytic N-terminal fragments of Htt form insoluble deposits in both the cytoplasm and nucleus, provoking the idea that mutHtt (mutant Htt) causes transcriptional dysfunction. While a number of specific transcription factors and co-factors have been proposed as mediators of mutHtt toxicity, the causal relationship between these Htt/transcription factor interactions and HD pathology remains unknown. Previous work has highlighted REST [RE1 (repressor element 1)-silencing transcription factor] as one such transcription factor. REST is a master regulator of neuronal genes, repressing their expression. Many of its direct target genes are known or suspected to have a role in HD pathogenesis, including BDNF (brain-derived neurotrophic factor). Recent evidence has also shown that REST regulates transcription of regulatory miRNAs (microRNAs), many of which are known to regulate neuronal gene expression and are dysregulated in HD. Thus repression of miRNAs constitutes a second, indirect mechanism by which REST can alter the neuronal transcriptome in HD. We will describe the evidence that disruption to the REST regulon brought about by a loss of interaction between REST and mutHtt may be a key contributory factor in the widespread dysregulation of gene expression in HD.

journal_name

Biochem Soc Trans

journal_title

Biochemical Society transactions

authors

Bithell A,Johnson R,Buckley NJ

doi

10.1042/BST0371270

subject

Has Abstract

pub_date

2009-12-01 00:00:00

pages

1270-5

issue

Pt 6

eissn

0300-5127

issn

1470-8752

pii

BST0371270

journal_volume

pub_type

杂志文章,评审

在线工具

Transcriptional dysregulation of coding and non-coding genes in cellular models of Huntington's disease.