Spinocerebellar ataxia protein (ATXN) (ATXN)

Spinocerebellar ataxia proteins, primarily known as Ataxins, are a diverse group of proteins whose mutations—most commonly polyglutamine (polyQ) expansions—lead to the progressive neurodegenerative disorders known as Spinocerebellar Ataxias (SCAs) [2, 12]. These proteins normally function in critical cellular processes such as RNA metabolism, deubiquitination, and transcriptional regulation [5, 8, 19]. In disease states, the expanded polyQ tracts cause the proteins to misfold and aggregate, leading to a toxic gain-of-function that results in the degeneration of Purkinje cells in the cerebellum and other neurons [6, 16, 22]. Therapeutic strategies currently focus on reducing the levels of these mutant proteins using antisense oligonucleotides (ASOs), RNA interference (RNAi), and gene therapy to halt or reverse disease progression [10, 15, 24]. While no disease-modifying treatments are currently approved, several candidates are in clinical and preclinical development, with biomarkers like neurofilament light chain (NfL) being used to monitor efficacy [3, 4, 7, 9].

Other names

AtaxinSCA proteinSpinocerebellar ataxia-associated proteinATXN protein

Antisense oligonucleotide-mediated mRNA degradation and RNA interference-mediated gene silencing to reduce levels of mutant proteins and mitigate toxic gain-of-function [6, 10, 15, 24]; symptomatic relief via modulation of ion channel activity [12, 13].