Buck Institute Logo The progressive neuro – degenerative genetic disorder, Huntington’s disease (HD) seemingly hampers motor coordination and paves way for cognitive decline along with dementia. It is believed that a mutation in the huntingtin (Htt) gene leads to the accumulation of toxic proteins further triggering neuronal cell death. Enzymes breaking down cells, termed as caspases, appear as a hallmark in the cascade of events occurring during HD neuronal death. Well, researchers have detected three small molecules which inhibit the activity of caspases. This restriction of caspases may curb toxicity and save neurons from cell death in cell culture.

As a part of the investigation, scientists employed a substrate based screening method which pointed out the compounds that react with caspases. On the basis of the reactions observed, the compounds were supposedly converted into caspase inhibitors. The developed inhibitors are possibly based on properties of a drug beneficial in treating human liver preservation injury. Such molecules seemingly cross the blood-brain barrier and act selectively to block the processes involved in HD.

The caspase inhibitors allegedly suppressed the proteolysis of Htt and rescued HD neurons that had begun to go through cell death. Dr. Lisa Ellerby, Ph.D. and colleagues assume that the introduced model is important in the battle against HD. Currently the caspase inhibitor acting selectively against the toxic effects of the Htt mutation is believed to be under wraps.

The research is published in Chemistry and Biology.