Kinase Mutations in Dominant Form of Spinocerebellar Ataxia (SCA)

To date, 31 genes associated with different forms of SCA have been identified, but the cellular and molecular bases for this pathology remain poorly defined. The autosomal dominant cerebellar ataxias (ADCA) were thought to be exclusively due to expansions of coding CAG repeats, as in the genes that underlie SCA1, SCA2, SCA3, SCA6, SCA7, SCA17, and DRPLA (dentatorubropallidoluysian atrophy)—the so-called polyglutamine expansion SCAs. About 90 % of genetically diagnosed ADCA is attributed to polyglutamine expansion SCAs [1]. However, mutations in two different kinase coding genes have been discovered in ADCA families: tau-tubulin-kinase 2 (TTBK2) in SCA11 and protein kinase c gamma (PKCγ) in SCA14. The roles of these two kinases are essential for post-translational modifications controlling neuronal degeneration or functional maintenance and, very interestingly, these kinases or their isoforms share common signaling pathways with another SCAs or neurodegenerative diseases. In this short communication, I introduce these two interesting ADAC causative kinases, their molecular signaling pathways leading to degeneration, and our published data on the topics.