Huntington’s disease which appears in people in their thirties or forties at present has no cure. This ailment which begins with jerky movements of the arms and legs may end up hampering motor skills including talking, swallowing and concentration of the patients. It can also lead to dysfunction and death of brain cells. A latest research undertaken by the University of Melbourne seems to expose the behavior of the mutant protein ‘huntingtin’ causing the Huntington’s disease.
The result that may enlighten possible targets for treating the disorder was conducted by employing a technology known as analytical ultracentrifugation. This allowed the scientists to track down the way human mutant ‘huntingtin’ proteins form into large clumps. These clumps are believed to destroy brain cells and cause progressed Huntington’s disease.
Dr Danny Hatters added, “Steps prior to the clustering of the mutated proteins were thought to damage cells, but these steps were not clearly detectable under a microscope. Understanding this process and finding the right target to block the ultimate death of the brain cells has been extremely difficult to determine.â€
Throughout the research, experts utilized the analytical ultracentrifugation technology and the methodology developed by them to picture this process in much greater detail. Claimed to be a novel discovery, the researchers revealed mutated huntingtin protein to develop three different sized clusters in the destroyed cells. This identification can possibly help investigators to develop new and better targeted treatment that close down the key processes allowing clusters to form and for the disease to progress.
Dr Hatters said, “Why it takes so long for the cells to die in human disease is not known – however it could be that cells eventually cannot compensate anymore from the process where toxicity is built up to form one cluster called oligomers. The real key of our work is that we now have direct targets in the critical steps in the process of cell toxicity and death and to gauge any therapeutic effects of drugs on these targets. We can also measure how this alleviates cellular toxicity and brain cell death. Importantly our research techniques could have application in assisting to find drug targets for other neurodegenerative diseases where toxic clusters of proteins play a role in the progression of the disease, such as for Parkinson’s disease.â€
It was assumed that small clusters of the mutant protein keep on gathering till they are in abundance and finally kill the brain cells. But the latest research determines these clusters to be static i.e. to be formed in a more complex way. An even amount of stress is apparently laid on cells by the clusters, instead of gathering slowly until they reach a ‘toxic’ level.
The research is published in the current issue of the Journal of Biological Chemistry.