Selective colocalization of transglutaminase-like activity in ubiquitinated intranuclear inclusions of hereditary dentatorubral-pallidoluysian atrophy

To investigate the role of transglutaminase (TG) in the pathophysiology of dentatorubral-pallidoluysian atrophy (DRPLA), the distributions of ubiquitin-positive neuronal intranuclear inclusions (Ub-NII) and TG activity were studied in three patients with DRPLA and four disease controls. In the cerebellar granule cells of DRPLA, 2.5-4.9% of neurons had Ub-NII, and 7.5-9.8% of them were TG positive. In the frontal cortex; however, the ratio of neurons with Ub-NII was relatively low compared with those in the cerebellar cortex, and no Ub-NII was TG positive. There was no distinct difference in the ratio of neurons with Ub-NII and their TG positivity between the cases with homozygous or heterozygous DRPLA patients. The selective and good colocalization of Ub-NII and TG in the cerebellar granule cells may reveal a role of TG in the neurodegenerative process in DRPLA.