Abstract:
:Fourteen neurological diseases have been associated with the expansion of trinucleotide repeat regions. These diseases have been categorized into those that give rise to the translation of toxic polyglutamine proteins and those that are untranslated. Thus far, compelling evidence has not surfaced for the inclusion of a model in which a common mechanism may participate in the pathobiology of both translated and untranslated trinucleotide diseases. In these studies we show that a double-stranded RNA-binding protein, PKR, which has previously been linked to virally-induced and stress-mediated apoptosis, preferentially binds mutant huntingtin RNA transcripts immobilized on streptavidin columns that have been incubated with human brain extracts. These studies also show, by immunodetection in tissue slices, that PKR is present in its activated form in both human Huntington autopsy material and brain tissue derived from Huntington yeast artificial chromosome transgenic mice. The increased immunolocalization of the activated kinase is more pronounced in areas most affected by the disease and, coupled with the RNA binding results, suggests a role for PKR activation in the disease process.
journal_name
Hum Mol Genetjournal_title
Human molecular geneticsauthors
Peel AL,Rao RV,Cottrell BA,Hayden MR,Ellerby LM,Bredesen DEdoi
10.1093/hmg/10.15.1531subject
Has Abstractpub_date
2001-07-15 00:00:00pages
1531-8issue
15eissn
0964-6906issn
1460-2083journal_volume
10pub_type
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