Intracellular inclusions, pathological markers in diseases caused by expanded polyglutamine tracts?

The largest group of currently known trinucleotide repeat diseases is cause d by (CAG)(n) repeat expansions. These (CAG)(n) repeats are translated into polyglutamine tracts from both mutant and wild type alleles. Genetic and t ransgenic mouse data suggest that the expanded poly-glutamines cause diseas e by conferring a novel deleterious gain of function on the mutant protein. These mutations are associated with the formation of intracellular inclusi ons. This review will consider findings from necropsy studies of human pati ents and transgenic mouse models of these diseases, along with in vitro mod els, in order to try to synthesise the current understanding of these disea ses and the evidence for and against inclusion formation as a primary mecha nism leading to pathology.