Ataxin-8 Activators

Ataxin-8 is a protein associated with a specific form of spinocerebellar ataxia (SCA), known as SCA8. This neurodegenerative disorder is characterized by progressive problems with coordination and balance, resulting from the degeneration of the cerebellum and its connections. The Ataxin-8 protein is encoded by the ATXN8 gene, which is located on chromosome 13.The defining feature of Ataxin-8 is the presence of an abnormally expanded CAG trinucleotide repeat within the coding region of the gene. In unaffected individuals, the number of CAG repeats in the ATXN8 gene is typically within a normal range; however, in individuals with SCA8, the CAG repeat is expanded beyond a critical threshold. This expansion translates into an elongated polyglutamine (polyQ) tract within the Ataxin-8 protein.

Proteins with expanded polyQ tracts, like Ataxin-8, have a propensity to misfold and form insoluble aggregates within neurons. These aggregates are believed to lead to cellular dysfunction and ultimately cell death, particularly in the nervous system. The precise mechanisms through which Ataxin-8 causes neurodegeneration are not fully understood, but it is thought to involve disruptions in various cellular processes, including transcription regulation, protein homeostasis, and axonal transport.