Self-Perpetuating Structural States in Biology, Disease, and Genetics (2002) / Chapter Skim
Currently Skimming:
Molecular chaperones as modulators of polyglutamine protein aggregation and toxicity
Molecular chaperones as modulators of polyglutamine protein aggregation and toxicity
Pages 36-42
The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.
From page 36... ...
These recent findings suggest that an imbalance between the neuronal chaperone capacity and the production of potentially dangerous polyQ proteins may trigger the onset of polyQ disease. Expansions of CAG trinucleotide repeats encoding polyglutamine (polyQ)
|
From page 37... ...
In transgenic mice expressing polyQ-expanded HD exon 1, neuronal inclusions containing aggregated HD protein form before the onset of neurological symptoms (16~. Regulated expression of HD exon 1 in a conditional transgenic mouse model resulted in a progressive neurological phenotype with polyQ inclusions in the striatum and cortex (34~.
|
From page 38... ...
Transcriptional Dysregulation by polyQ Aggregation Analyzing the cellular components contained in neuronal polyQ inclusions may offer valuable clues as to how polyQ expansions cause cellular dysfunction. To date, numerous proteins have been shown to be sequestered into the inclusions using immunohistochemical and biochemical approaches.
|
From page 39... ...
Intermediates of polyQ aggregation recruit essential transcription factors, thereby inhibiting theirtranscriptional activities and causing cellular dysfunction. The Hsp70/Hsp40 chaperone system prevents this recruitment and thus mitigates polyQ toxicity.
|
From page 40... ...
1~. Considering that overexpression of HsplO4 also suppresses polyQ aggregation, it is possible that excess amounts of the chaperone, in cooperation with Hsp70/ Hsp40, effectively dissociate polyQ oligomers that nucleate the aggregation process (Fig.
|
From page 41... ...
However, the exact mechanisms by which expanded polyQ proteins exert cellular toxicity remain to be established. In testing current hypotheses, it will be important to dissect the process of polyQ aggregation into distinct steps.
|
From page 42... ...
15. Nucifora, F
|
Key Terms
This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More
information on Chapter Skim is available.