Ataxin

Ataxin refers to a family of intracellular proteins encoded by various ATXN genes. These proteins are diverse in their tissue distribution and cellular roles, but many are associated with the regulation of transcription, RNA processing, and protein quality control. The exact functions of several Ataxin family members are still being studied, and their roles can vary between individuals and tissues.

A major clinical relevance of ataxins is their involvement in spinocerebellar ataxias (SCAs), a group of dominantly inherited neurodegenerative disorders. The diseases are typically caused by expansions of CAG trinucleotide repeats in certain ATXN genes, which produce elongated polyglutamine tracts in the corresponding ataxin proteins. Classic examples include ATXN1 (SCA1), ATXN2 (SCA2), ATXN3 (SCA3/Machado-Joseph disease), and ATXN7 (SCA7). The resulting toxic proteins contribute to progressive degeneration of the cerebellum and related neural pathways, leading to symptoms such as gait and limb ataxia, dysarthria, nystagmus, coordination difficulties, and in some cases cognitive impairment. The age of onset and disease severity typically correlate with the length of the repeat expansion, and inheritance is autosomal dominant.

Diagnosis relies on clinical evaluation supported by genetic testing to identify pathogenic ATXN repeat expansions. Neuroimaging may show cerebellar atrophy. There is no cure for most SCAs; management is supportive and multispecialty, focusing on physical and occupational therapy, speech therapy, and management of symptoms. Research is advancing in approaches to reduce mutant ataxin expression, including antisense therapies and gene-silencing strategies, offering potential avenues for disease modification in the future.