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.