Calcium homeostasis and spinocerebellar ataxia-1 (SCA-1)

Spinocerebellar ataxia-1 (SCA-1) belongs to a group of polyglutamine neurodegenerative disorders characterized by the expansion of a glutamine tract within the mutant disease-causing protein. In SCA-1, the expression of mutant ataxin-1 induces a progressive functional loss and the subsequent degeneration of a set of neurons including cerebellar Purkinje cells. Studies on SCA-1 transgenic mice have provided further understanding of the molecular and cellular events important for the disease. This review discusses what has been learned about the pathogenesis of SCA-1 through the transgenic mouse models in reference to Ca(2+) dependent pathways. This article also discusses the role of Ca(2+) regulating cytoplasmic and nuclear proteins in the pathogenesis of SCA-1. Finally, we discuss the use of double mutant mouse models to understand the association between Ca(2+) binding proteins and Purkinje cell pathology in SCA-1.