Finding a cure for Huntington’s disease by boosting degradation of toxic proteins

Investigating the degradation mechanisms of mutant huntingtin proteins

One of the ways in which a protein is degraded is through a process that labels them for destruction, the equivalent of the ‘kiss of death’ for a protein. This clearance system involves two successive steps: tagging of the protein to be eliminated by the attachment of molecules called ubiquitin, and subsequent degradation of the tagged protein. According to Dr. Katrin Jünemann’s previous work, this mechanism is at the heart of Huntington’s disease. “My past research clearly showed that mHtt ubiquitination and clearance appears to be inefficient, leading to accumulation of the toxic mHtt ,” she explains. Building on this knowledge, Dr. Jünemann intends to thoroughly study the precise molecular mechanisms of mHtt ubiquitin tagging and degradation in an age-dependent manner. Her methodology will include working with a worm called C. elegans. These model organisms exhibit the same symptoms as humans when given the mutated gene. They are particularly valuable to studies on neurodegenerative diseases because of their short lifespan.

“Never before has the population of the world been so old,” stresses Dr. Jünemann. “Neurodegenerative diseases represent an increasingly pressing issue, not only regarding health, but also society, economy and politics. However, compared to other research fields, such as cancer or heart disease, funds dedicated to ND are insufficient in regard to the number of cases and the societal cost.” With her research, Dr. Katrin Jünemann aims to contribute to a better understanding of Huntington’s disease and, by extension, of other comparable neurodegenerative diseases. The ultimate goal is to develop a treatment capable of delaying, if not preventing, the onset of symptoms in patients diagnosed with the mutated gene.