Current understanding on the pathogenesis of polyglutamine diseases

Abstract

Abstract: Polyglutamine (polyQ) diseases are a family of neurodegenerative disorders including Huntington's disease, spinobulbar muscular atrophy, dentatorubral-pallidoluysian atrophy and several spinocerebellar ataxias. polyQ diseases are caused by abnormal expansion of CAG repeats in certain genes. The expanded CAG repeats are then translated into a series of abnormally expanded polyQ tracts. Such polyQ tracts may induce misfolding of the disease-causing proteins. The present review mainly focuses on the common characteristics of the pathogenesis of these polyQ diseases, including conformational transition of proteins and its influence on the function of these proteins, the correlation between decreased ability of proteolysis and late-onset polyQ diseases, and the relationship between wide expression of disease-causing proteins and selective neuronal death.