Polyglutamine expansion diseases are inherited neurodegenerative disorders caused by the expansion of CAG repeat mutations in the coding region of genes encoding for specific proteins, mostly of unknown function. One example is Machado-Joseph disease (MJD) or spinocerebellar ataxia 3, which was described in people of Portuguese descendents and is caused by expanded ataxin-3, a polyubiquitin-binding protein. Like other neurodegenerative diseases, MJD exhibits gradual progression of symptoms that finally result in the death of the patients. Despite the identification of the genetic defects, the molecular mechanisms by which the mutant protein initiates the pathogenic process remain to be elucidated. This chapter resumes some of the most important features of polyglutamine expansion diseases with a special emphasis on MJD pathogenesis. Particular relevance is given to ataxin-3 structure and function, the formation of aggregates of mutant ataxin-3, the characteristics of current disease animal models and the most recent therapeutic strategies proposed for the treatment of MJD.
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Ribeiro, S.M., Almeida, L.P.d., Carvalho, A.L., Rego, A.C. (2007). Polyglutamine Expansion Diseases – the Case of Machado-Joseph Disease. In: Malva, J.O., Rego, A.C., Cunha, R.A., Oliveira, C.R. (eds) Interaction Between Neurons and Glia in Aging and Disease. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-70830-0_18
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