Neurotherapeutics

, Volume 4, Issue 2, pp 285–294

Molecular pathogenesis of spinocerebellar ataxia type 6

Article

DOI: 10.1016/j.nurt.2007.01.003

Cite this article as:
Kordasiewicz, H.B. & Gomez, C.M. Neurotherapeutics (2007) 4: 285. doi:10.1016/j.nurt.2007.01.003

Summary

Spinocerebellar ataxia type 6 (SCA6) is a neurodegenerative disorder caused by abnormal expansions of a trinucleotide CAG repeat in exon 47 of the CACNA1A gene, which encodes the cdA subunit of the P/Q-type voltage-gated calcium channel. The CAG repeat expansion is translated into an elongated polyglutamine tract in the carboxyl terminus of the α1A subunit. The α1A sub unit is the main pore-forming subunit of the P/Q-type calcium channel. Patients with SCA6 suffer from a severe form of progressive ataxia and cerebellar dysfunction. Design of treatments for this disorder will depend on better definition of the mechanism of disease. As a disease arising from a mutation in an ion channel gene, SCA6 may behave as an ion channelopathy, and may respond to attempts to modulate or correct ion channel function. Alternatively, as a disease in which the mutant protein contains an expanded polyglutamine tract, SCA6 may respond to the targets of drug therapies developed for Huntington’s disease and other polyglutamine disorders. In this review we will compare SCA6 to other polyglutamine diseases and channelopathies, and we will highlight recent advances in our understanding of α1A subunits and SCA6 pathology. We also propose a mechanism for how two seemingly divergent hypotheses can be combined into a cohesive model for disease progression.

Key Words

Spinocerebellar ataxia type 6 (SCA6) channelopathy polyglutamine disease P/Q-type calcium channel Purkinje cell cerebellum 

Copyright information

© Springer New York 2007

Authors and Affiliations

  1. 1.Ludwig Institute for Cancer ResearchUniversity of California at San DiegoLa Jolla
  2. 2.Department of NeurologyUniversity of ChicagoChicago

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