ABSTRACT
The triplet repeat diseases are caused by expansions of triplet repeat, which can be located either within or outside of the open reading frame. This chapter focuses on diseases caused by repeats encoding polyglutamine and polyalanine tracts. Consequently, Huntington disease remains an important model and inspiration for other, often more complex, diseases associated with aggregate-prone proteins. Expansions or duplications of polyalanines are primary mutations in nine different diseases. The main advantage of Drosophila disease models is the availability of genetic tools that facilitate the determination of molecular mechanisms involved in a particular disease. Thus, valuable lessons about the diseases and possible therapies can be learned from Drosophila models. Glycogen synthase kinase-3 (GSK3) is a kinase involved in tau phosphorylation and inhibition of GSK3 activity led to a decrease in tau toxicity in mouse and fly models of tauopathies, accompanied by decreased tau phosphorylation.
