Nuclear accumulation of polyglutamine disease proteins and neuropathology.
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.
Havel
Lauren S
LS
Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA. lrsmit4@emory.edu
Li
Shihua
S
Li
Xiao-Jiang
XJ
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D006801:Humans; D050505:Mutant Proteins / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000378:metabolism* / Q000473:pathology*; D010455:Peptides / Q000378:metabolism*; D019680:Trinucleotide Repeat Expansion
D050505:Mutant Proteins; D010455:Peptides; C097188:polyglutamine