[Polyglutamine diseases: a pathologic view]

It has been widely accepted that there is a discrepancy between clinical features and lesion distribution evaluated by neuronal loss in the polyglutamine diseases including Huntington's disease and dentatorubral-pallidoluysian atrophy (DRPLA). Neuronal intranuclear inclusion (NII) is a characteristic feature of the polyglutamine diseases; however, its significance in the pathogenesis is still a matter of controversy. In a study of DRPLA brains, we found that intranuclear diffuse accumulation of mutant proteins with expanded polyglutamine stretches is another pathology involving many neurons in various nervous system regions including the dentatorubral and pallidoluysian systems, in which the number of affected neurons was constantly high. Of note was that affected neurons in some regions such as the cerebral cortex extremely vary in number depending on the size of CAG repeat, suggesting that these situations may be responsible for a variety of phenotypes including dementia in DRPLA. The nuclear pathology was also detectable in a wide range of CNS regions in Machado-Joseph disease and Huntington's disease. The nuclear pathology may be a characteristic feature and exert certain influence on certain nuclear functions of many neurons in the polyglutamine diseases.