Interaction between neuronal intranuclear inclusions and promyelocytic leukemia protein nuclear and coiled bodies in CAG repeat diseases

Neuronal intranuclear inclusions (NIIs) are a pathological hallmark of CAG repeat diseases. To elucidate the influence of NII formation on intranuclea r substructures, we investigated the relationship of NIIs with nuclear bodi es in brains of dentatorubral-pallidoluysian atrophy and Machado-Joseph dis ease. in both diseases, promyelocytic leukemia protein, a major component o f the promyelocytic leukemia protein nuclear bodies, altered the normal dis tribution and was rearranged around NH, forming a single capsular structure . We further demonstrated that NIIs were present in close contact with coil ed bodies, a highly dynamic domain that may be involved in the biogenesis o f small nuclear ribonucleoproteins. The preferential association of intranu clear polyglutamine aggregates with coiled bodies was also confirmed in the dentatorubral-pallidoluysian atrophy transgenic mouse brain and culture ce lls expressing mutant atrophin-1. The results suggest that the interaction between NIIs and nuclear bodies may play a role in the pathogenesis of CAG repeat diseases.