Clévio Nóbrega

Polyglutamine disorders (polyQ) are a group of inherited neurodegenerative diseases with a fatal outcome. They are caused by an abnormal expansion of a coding trinucleotide repeat (CAG), which is then translated in an abnormal protein with an elongated glutamine tract (Q). Until now, nine polyQ disorders are known and described: dentatorubral- pallidoluysian atrophy (DRPLA), Huntington’s disease (HD), spinal-bulbar muscular atrophy (SBMA), and six spinocerebellar ataxias (SCA 1, 2, 3, 6, 7, and 17). The genetic basis of polyQ disorders is well established and described, and despite important progresses, opening the possibility to generate genetic models of the disease, the mechanisms accounting for neuronal degeneration are still largely unknown and there is currently no treatment available for these disorders. In fact, it is believed that the different polyQ can share some mechanisms and pathways contributing to neurodegeneration and to the disease progression. With this book we want to review the current knowledge about the polyQ disorders, focusing in two main aspects: (1) the mechanisms underlying the pathology development and progression, and (2) the therapeutic strategies that are being studied to stop or delay the disease progression.