| Affiliation: | (1) Department of Pathology, Brain Research Institute, Niigata University, 1 Asahimachi, Niigata 951-8585, Japan;(2) Department of Comparative and Experimental Medicine, Brain Research Institute, Niigata University, Niigata, Japan;(3) Department of Neurology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan |
| Abstract: | Machado-Joseph disease (MJD), also called spinocerebellar ataxia type 3, is caused by mutant ataxin-3 with a polyglutamine expansion. Although there is no treatment available at present to cure or delay the onset of MJD, mouse models have been generated to facilitate the development of a therapy. In this review, the published reports on mouse models of MJD and other polyglutamine spinocerebellar ataxias are compared. Based on these studies, the following approaches will be discussed as candidate treatments for MJD: 1) interfering with the formation of the mutant ataxin-3 cleavage fragment and possibly aggregate or inclusions, 2) reducing the disease protein nuclear localization, and 3) decreasing mutant ataxin-3 expression in neurons. |
