Cutting errors
Although the exact cause of Huntington disease (HD) pathophysiology is unknown, a recent study suggests that inefficient proteolysis may lie at the root of the problem. HD is an autosomal-dominant neurodegenerative disorder characterized by involuntary movements and cognitive impairment leading to dementia, due to loss of brain neurons. The genetic defect causing HD is an expansion of an amino-acid stretch in a protein called huntingtin. Analysis of mutant huntingtin has attracted much attention among researchers since its discovery in 1993. In the November issue of Nature Genetics, Dyer and McMurray show that mutant huntingtin protein is resistant to cleavage by caspase enzymes. This results in an accumulation of mutant protein in cells, interfering with the function of the normal huntingtin protein. The results indicate that HD neurodegeneration might be caused by loss of function of normal huntingtin, rather than a direct action of the mutant protein. Confirmation of this model awaits testing of mice with conditional disruptions in HD activity.
This is a preview of subscription content, access via your institution
