The role of the CACNA1A gene in the pathogenesis of episodic ataxia 2 and spinocerebellar ataxia 6

CACNA1A encodes for the voltage-gated calcium channel CaV2.1. Mutations to CACNA1A are known to cause an assortment of disorders, including episodic ataxia 2, spinocerebellar ataxia 6, familial hemiplegic migraine 1, and more. The pathogenic nature behind these mutations is still unknown, but recent studies have given new information that points toward certain conclusions. In particular, episodic ataxia 2 appears to be caused (in some mutations) by misfolding and improper trafficking of both wild-type and mutant CaV2.1 channels. Spinocerebellar ataxia 6 is more complicated, as recent findings of the bicistronic nature of CACNA1A may mean that the disorder is more akin to a polyglutamine disease than a channelopathy. The goal of this thesis is to review the literature available that addresses these disorders and their progression, as well as future treatment strategies