Increased apoptosis of Huntington disease lymphoblasts associated with repeat length-dependent mitochondrial depolarization

Publisher Website
Google Scholar
Abstract
Huntington disease (HD) is a genetically dominant condition caused by expanded CAG repeats coding for glutamine in the HD gene product huntingtin1. Although HD symptoms reflect preferential neuronal death in specific brain regions, huntingtin is expressed in almost all tissues2, so abnormalities outside the brain might be expected. Although involvement of nuclei3,4,5,6,7 and mitochondria8,9,10,11,12,13,14 in HD pathophysiology has been suggested, specific intracellular defects that might elicit cell death have been unclear. Mitochondria dysfunction is reported in HD brains10,11,12,13; mitochondria are organelles that regulates apoptotic cell death15,16. We now report that lymphoblasts derived from HD patients showed increased stress-induced apoptotic cell death associated with caspase-3 activation. When subjected to stress, HD lymphoblasts also manifested a considerable increase in mitochondrial depolarization correlated with increased glutamine repeats.