For a protein of any kind to work properly, it must fold into a three dimensional configuration, which then allows it to interact with cell receptors, cellular machinery and other proteins. Heat shock proteins impact HD when the huntingtin protein, which contains the disease conferring expanded CAG repeat, becomes misfolded. If chaperones can assist mutant huntingtin protein to fold properly, it may not continue along a path that leads to degeneration. Early data indicates that experiments that increase this chaperone activity lead to a decrease in neurodegeneration in cell models, fly and worm models of polyglutamine repeat disease. In addition to aggregations and chaperones, caspases are an area of intense study.
Caspases are proteins that play a role in cell death.
Research has proven that by inhibiting caspase activity, you can delay the onset of HD in transgenic mice. Several Coalition labs presented their work on how different caspases affect neurodegeneration. In addition to each presentation by Coalition labs, the Investigators and Sub-Committee members met in a closed session to determine the future goals for the Coalition and the direction for new HD research initiatives. An assay is a method used to determine whether your work has caused the desired effect in an experiment, such as curtailing the aggregation process or preventing cell death. An example of a high throughput screen is the work currently being conducted by HDSA sponsored investigator, Dr. Erich Wanker, at the Max-Planck Institute in Germany.