Ataxin 1

Ataxin 1 (ATXN1) is a protein encoded by the ATXN1 gene in humans. It is primarily known for its role in the pathogenesis of spinocerebellar ataxia type 1 (SCA1), a neurodegenerative disorder.

Function:

Ataxin 1 is a nuclear protein involved in transcriptional regulation. It interacts with other proteins, including Capicua (CIC) and the RNA splicing factor RBM17, forming a transcriptional repressor complex that regulates gene expression. This complex is important for neuronal development and function, particularly in the cerebellum. Ataxin 1 is also involved in RNA processing and metabolism. The precise normal function of Ataxin 1 is still being investigated.

Gene and Location:

The ATXN1 gene is located on human chromosome 6p23. The gene contains a CAG trinucleotide repeat sequence in its coding region.

Role in Disease (Spinocerebellar Ataxia Type 1 - SCA1):

SCA1 is caused by an abnormal expansion of the CAG repeat within the ATXN1 gene. Normally, this repeat sequence is between 6 and 39 repeats. In individuals with SCA1, the repeat is expanded to 40 or more repeats, resulting in a mutant Ataxin 1 protein with an abnormally long polyglutamine (polyQ) stretch. This expanded polyQ stretch causes the mutant Ataxin 1 protein to misfold and aggregate, forming intracellular inclusions within neurons, particularly in the cerebellum, brainstem, and spinal cord. These inclusions disrupt normal cellular function and eventually lead to neuronal degeneration, resulting in the characteristic symptoms of SCA1, which include progressive ataxia (lack of coordination), dysarthria (speech difficulties), and dysphagia (swallowing difficulties). The severity and age of onset of SCA1 are generally correlated with the length of the CAG repeat expansion.

Research Significance:

Ataxin 1 and its role in SCA1 are actively researched areas. Understanding the mechanisms by which mutant Ataxin 1 causes neuronal dysfunction and death is crucial for developing effective therapies for SCA1 and other polyglutamine expansion disorders. Research focuses on various aspects, including:

• Understanding the normal function of Ataxin 1.
• Identifying the specific mechanisms by which mutant Ataxin 1 causes toxicity.
• Developing therapeutic strategies to reduce the levels of mutant Ataxin 1, prevent its aggregation, or ameliorate its toxic effects.