Huntingtin Interacting Proteins and Neurodegeneration
Author Information
Author(s): Kaltenbach Linda S, Romero Eliana, Becklin Robert R, Chettier Rakesh, Bell Russell, Phansalkar Amit, Strand Andrew, Torcassi Cameron, Savage Justin, Hurlburt Anthony, Cha Guang-Ho, Ukani Lubna, Chepanoske Cindy Lou, Zhen Yuejun, Sahasrabudhe Sudhir, Olson James, Kurschner Cornelia, Ellerby Lisa M, Peltier John M, Botas Juan, Hughes Robert E
Primary Institution: Prolexys Pharmaceuticals
Hypothesis
Genetic modifiers of Huntington's disease neurodegeneration should be enriched among huntingtin protein interactors.
Conclusion
The study identified 27 high-confidence genetic modifiers of neurodegeneration from a set of 60 genes tested in a Drosophila model.
Supporting Evidence
- Identified 234 high-confidence huntingtin-associated proteins.
- 27 of 60 orthologs tested were high-confidence genetic modifiers.
- 45% hit rate for genetic modifiers among interactors is significantly higher than typical unbiased genetic screens.
Takeaway
Researchers found that some proteins that interact with the huntingtin protein can help protect against the damage caused by Huntington's disease.
Methodology
The study used high-throughput yeast two-hybrid screening and affinity pull-down followed by mass spectrometry to identify huntingtin interactors.
Limitations
The study may contain false positives and does not represent all binding proteins.
Statistical Information
P-Value
≤0.05
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
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