Small ubiquitin-like modifiers (SUMOs) are proteins homologous to ubiquitin that possibly regulate intranuclear protein localization, nuclear transport, and ubiquitination. We examined patients of DRPLA, SCA1, MJD, and Huntington's disease and found that neurons in affected regions of the brain react strongly to SUMO-1, a family member of SUMOs. Western blot with a transgenic mouse expressing mutant ataxin-1 showed the increase of SUMOylated proteins in the cerebellar cortex, which we named ESCA1 and ESCA2. These results indicated activation of SUMO-1 system in polyglutamine diseases and predicted its involvement in the pathology.