Questions Remain Implications of the experiments are both basic and applied. Our work provides a molecular explanation for all polyglutamine diseases. But CBP is not the only other protein involved. Still, the tango between huntingtin and CBP reveals a potentially powerful drug target. The new findings provide a piece to an ever-expanding pathogenic puzzle.
Questions remain however, such as just how mutant huntingtin slithers into the nucleus.
Huntingtin is normally in the cytoplasm, but the pathological form gets into the nucleus. I think maybe it is truncated first, leaving a piece with the poly-glutamines. Mutant huntingtin also grabs CBP in the cytoplasm, where proteins are synthesized. Ongoing work in many labs seeks to sort out how the polygln disorders are alike and how they differ. The obvious, and probably most important factor is the particular protein context in which each of the expanded polygln domains reside.