Neuronal intranuclear inclusions have become the neuropathological signature of the CAG repeat diseases, although their cytotoxicity is a matter of controversy. It has been demonstrated that the inclusions in dentatorubral-pallidoluysian atrophy (DRPLA) and Machado-Joseph disease (MJD) were immunopositive for several transcription factors such as TATA-binding protein (TBP), TBP-associated factor (TAF(II)130), Sp1, cAMP-responsive element-binding protein (CREB) and CREB-binding protein, suggesting that neuronal degeneration in polyglutamine diseases may result from nuclear depletion of transcription factors containing the glutamine-rich domain. It was also revealed that, in the DRPLA brain, expanded polyglutamine stretches were diffusely accumulated in neuronal nucleoplasm. This nuclear pathology involved many neurons in various nervous system regions, such as the cerebral cortex, thalamus, substantia nigra, pontine nuclei, reticular formation and inferior olive, in addition to the previously recognized affected regions. The diffuse nuclear labeling was also detected in MJD, Huntington's disease, and spinal and bulbar muscular atrophy, suggesting that this nuclear pathology may be a characteristic feature and may exert certain influence on certain nuclear functions of many neurons in the CAG repeat diseases.