ATXN2 Identified as New Genetic Risk Factor for Lou Gehrig's Disease (ALS)

Fri, 11/19/2010 - 05:30

Ataxin antibodies are used in the study of autosomal dominant cerebellar ataxia (ADCA) diseases. These neurodegenerative disorders are highly heterogeneous, characterized by progressive, irreversible, atrophy of the cerebellum and spinal cord.

Ataxin 2 is encoded by the ATXN2 gene, mutation of which can lead to Spinocerebellar Ataxia Type 2 (SCA2). Recently, Ataxin-2 antibodies were used in an international study that showed ATXN2 to be a genetic risk factor in another neurodegenerative disorder - Amyotrophic lateral sclerosis (ALS) or Lou Gehrig's disease. The mutation causing SCA2 is identified by expanded CAG repeats in the coding region of ATXN2. The expansion is extremely variable in size, but averages 34-52 repeats; it results in an elongated polyglutamine tract (called a polyQ expansion) in encoded Ataxin-2.

Immunocytochemistry/Immunofluorescence: Ataxin-2 Antibody

A team led by scientists from the University of Pennsylvania searched for similar mutations in the DNA of neurons from ALS patients. This followed earlier antibody research in yeast cells, which showed Ataxin-2 to modify toxicity of the gene TDP43. TDP-43 mutations are known to cause spinocerebellar ataxia with axonal neuropathy (SCAN1), as well as ALS. Antibody assays using a fruit fly model confirmed Ataxin-2 to be a potent TDP-43 modifier, with TDP-43 toxicity increasing comparative to the level of Ataxin-2 present.

In neurons of human ALS patients, it was discovered that Ataxin-2 underwent a PolyQ mutation similar to that of SCA2, with a strong genetic correlation between expanded CAG repeats and risk of ALS. The expansions were shorter than those of SCA2, but longer than controls. This newly-found association between ATXN2, TDP-43 and ALS is an exciting one, and we at Novus Biologicals anticipate a variety of new biomarkers being added to our antibody catalog.

Novus Biologicals offers many Ataxin-2 reagents for your research needs including:

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