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.
Vig
P J
PJ
Department of Neurology, University of Mississippi Medical Center, Jackson, MS 39216, USA. pvig@neurology.umsmed.edu
Subramony
S H
SH
McDaniel
D O
DO
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D020754:Spinocerebellar Ataxias / Q000235:genetics / Q000378:metabolism*
D002118:Calcium