ABSTRACT
In this chapter, the author describes clinical and molecular genetic aspects of Dentatorubral-pallidoluysian atrophy (DRPLA). The most notable clinical characteristic of the DRPLA is the considerable heterogeneity in clinical presentation depending on the age-of-onset. It should be noted that these variable phenotypes of DRPLA often appear even within the same family. Formation of peri—and intranuclear aggregates was observed in COS7 cells expressing truncated mutant DRPLA proteins with an expanded polyGln stretch, but not in COS7 cells expressing truncated wild-type DRPLA protein. Perutz and colleagues proposed that polyGln stretches may function as polar zippers by joining complementary proteins through hydrogen bonding, and that extensions of the polyGln stretches may result in tight joining and aggregation of the affected proteins. Although the suppression effect of transglutaminase inhibitors was partial, the results opened new prospects for developing therapeutic measures for the polyglutamine diseases.
