Mol Brain. 2009 Jul 3;2:21.

Nuclear accumulation of polyglutamine disease proteins and neuropathology.

Source

Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA. lrsmit4@emory.edu

Abstract

There are nine inherited neurodegenerative disorders caused by polyglutamine (polyQ) expansion in various disease proteins. Although these polyglutamine proteins have different functions and are localized in different subcellular regions, all the polyQ diseases share a common pathological feature: the nuclear accumulation of polyQ disease proteins and the formation of inclusions. The nuclear accumulation of polyQ proteins in turn leads to gene transcriptional dysregulation and neuropathology. Here we will discuss potential mechanisms behind the nuclear accumulation of mutant polyQ proteins, since an understanding of how polyQ proteins accumulate in the nucleus could help elucidate the pathogenesis of these diseases and develop their treatment.

PMID:: 19575804; [PubMed - indexed for MEDLINE]
PMCID: PMC2714308

Free PMC Article

Publication Types, MeSH Terms, Substances, Grant Support

Publication Types

MeSH Terms

Substances

Grant Support

LinkOut - more resources

Full Text Sources

Medical

Degenerative Nerve Diseases - MedlinePlus Health Information

Libraries

LinkOut Holdings

Supplemental Content

Related citations

Expanded polyglutamine domain possesses nuclear export activity which modulates subcellular localization and toxicity of polyQ disease protein via exportin-1. [Hum Mol Genet. 2011]
Expanded polyglutamine domain possesses nuclear export activity which modulates subcellular localization and toxicity of polyQ disease protein via exportin-1.
Chan WM, Tsoi H, Wu CC, Wong CH, Cheng TC, Li HY, Lau KF, Shaw PC, Perrimon N, Chan HY. Hum Mol Genet. 2011 May 1; 20(9):1738-50. Epub 2011 Feb 7.
Review Polyglutamine expansion diseases: failing to deliver. [Trends Mol Med. 2005]
Review Polyglutamine expansion diseases: failing to deliver.
Morfini G, Pigino G, Brady ST. Trends Mol Med. 2005 Feb; 11(2):64-70.
Review Polyglutamine and neurodegeneration: structural aspects. [Protein Pept Lett. 2004]
Review Polyglutamine and neurodegeneration: structural aspects.
Masino L. Protein Pept Lett. 2004 Jun; 11(3):239-48.
Review Expanded polyglutamine stretches lead to aberrant transcriptional regulation in polyglutamine diseases. [Hum Cell. 2001]
Review Expanded polyglutamine stretches lead to aberrant transcriptional regulation in polyglutamine diseases.
Shimohata T, Onodera O, Tsuji S. Hum Cell. 2001 Mar; 14(1):17-25.
Review Modifiers and mechanisms of multi-system polyglutamine neurodegenerative disorders: lessons from fly models. [J Genet. 2010]
Review Modifiers and mechanisms of multi-system polyglutamine neurodegenerative disorders: lessons from fly models.
Mallik M, Lakhotia SC. J Genet. 2010 Dec; 89(4):497-526.

See reviews... See all...

Cited by 1 PubMed Central article

Lack of interleukin-1 type 1 receptor enhances the accumulation of mutant huntingtin in the striatum and exacerbates the neurological phenotypes of Huntington's disease mice. [Mol Brain. 2010]
Lack of interleukin-1 type 1 receptor enhances the accumulation of mutant huntingtin in the striatum and exacerbates the neurological phenotypes of Huntington's disease mice.
Wang CE, Li S, Li XJ. Mol Brain. 2010 Nov 2; 3:33. Epub 2010 Nov 2.

Related information

Related Citations
Calculated set of PubMed citations closely related to the selected article(s) retrieved using a word weight algorithm. Related articles are displayed in ranked order from most to least relevant, with the “linked from” citation displayed first.
References for this PMC Article
Citation referenced in PubMed article. Only valid for PubMed citations that are also in PMC.
Substance (MeSH Keyword)
PubChem chemical substance (submitted) records that are classified under the same Medical Subject Headings (MeSH) controlled vocabulary as the current articles.
Free in PMC
Free full text articles in PMC
Cited in PMC
Full-text articles in the PubMed Central Database that cite the current articles.

Recent activity

Clear Turn Off Turn On

Nuclear accumulation of polyglutamine disease proteins and neuropathology.
Nuclear accumulation of polyglutamine disease proteins and neuropathology.
Mol Brain. 2009 Jul 3 ;2:21.

PubMed
Effect of ablated hippocampal neurogenesis on the formation and extinction of co...
Effect of ablated hippocampal neurogenesis on the formation and extinction of contextual fear memory.
Mol Brain. 2009 Jan 13 ;2:1.

PubMed
Dopamine D1 receptor-mediated NMDA receptor insertion depends on Fyn but not Src...
Dopamine D1 receptor-mediated NMDA receptor insertion depends on Fyn but not Src kinase pathway in prefrontal cortical neurons.
Mol Brain. 2010 Jun 22 ;3:20.

PubMed
In vivo multiplex quantitative analysis of 3 forms of alpha melanocyte stimulati...
In vivo multiplex quantitative analysis of 3 forms of alpha melanocyte stimulating hormone in pituitary of prolyl endopeptidase deficient mice.
Mol Brain. 2009 Jun 2 ;2:14.

PubMed
Welcome to molecular brain.
Welcome to molecular brain.
Mol Brain. 2008 Jun 17 ;1:1.

PubMed

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

PubMed

Display Settings:

Send to: