Chun et al. (page 25) provide convincing evidence that tissue transglutaminase (tTG) does not contribute to the formation of aggregates of huntingtin, a pathological hallmark of Huntington's disease. Previous in vitro studies suggested that mutant huntingtin is a substrate of tTG, leading some researchers to suggest that tTG could be a therapeutic target for treating the disease, which is caused by the expansion of a polyglutamine domain in the NH2-terminal region of huntingtin.
To test this hypothesis in vivo, Chun et al. transfected cultured human neuroblastoma cells with wild-type or mutant NH2-terminal huntingtin constructs. Huntingtin aggregates formed in cells expressing the mutant form of the protein, but tTG was completely excluded from the aggregates. The abundance and localization of the aggregates remained unaffected when tTG expression levels were significantly increased in the cells. In addition,...
