ataxins

Ataxins are a family of proteins encoded by genes associated with a group of rare, inherited neurodegenerative disorders known as spinocerebellar ataxias (SCAs). These disorders primarily affect the cerebellum and other regions of the nervous system, leading to progressive loss of coordination, balance, and speech. The term "ataxin" originates from the Greek word *ataxia*, meaning lack of order or coordination, reflecting the movement impairments characteristic of these conditions.

The most well-studied ataxins are the products of the *ATXN* genes, including ataxin-1, ataxin-2, ataxin-3, and ataxin-7, among others. These proteins share a common structural feature: an expanded polyglutamine (poly-Q) tract, a sequence of glutamine amino acids that exceeds a normal length. In healthy individuals, these tracts are relatively short, but in affected individuals, they are abnormally elongated due to genetic mutations, typically caused by trinucleotide repeat expansions (CAG repeats). The expanded poly-Q tracts disrupt normal protein function and promote toxic aggregation, contributing to neuronal degeneration.

Spinocerebellar ataxia type 1 (SCA1), caused by mutations in the *ATXN1* gene encoding ataxin-1, is one of the most studied forms. Similarly, SCA3 (also called Machado–Joseph disease) results from mutations in *ATXN3*, encoding ataxin-3. These disorders exhibit autosomal dominant inheritance, meaning that affected individuals typically inherit a single mutated copy of the gene from one parent. Symptoms vary depending on the specific ataxin involved but often include cerebellar ataxia, dysarthria (slurred speech), and progressive neurodegeneration.

Research into ataxins has advanced understanding of protein misfolding diseases, including Huntington’s disease and certain forms of amyotrophic lateral sclerosis (ALS). Therapeutic strategies targeting poly-Q aggregation or modifying protein function remain areas of active investigation, with potential implications for treating multiple neurodegenerative conditions.