Ataxin-2 (E3B3Z) Rabbit Monoclonal Antibody #35121

Spinocerebellar ataxia type 2 (SCA2), a lethal autosomal dominant neurodegenerative disorder, is characterized by slurred speech, loss of limb coordination, and gait abnormalities resulting from the degeneration of cerebellar Purkinje cells and a subset of brainstem neurons (1,2). SCA2 is caused by an excessive expansion of polyglutamine (polyQ) repeats at the N-terminal coding region of the ATXN2 gene, which encodes the protein ataxin-2 (2). Intermediate-length polyQ repeats in ATXN2 have also been identified as a risk factor for amyotrophic lateral sclerosis (ALS) (3-5). Ataxin-2 is a ubiquitously expressed RNA-binding protein (RBP) that plays an important role in RNA stability and translation (6,7). Ataxin-2 can undergo liquid-liquid phase separation and is frequently recruited to cytoplasmic foci known as stress granules (SGs), which are ribonucleoprotein (RNP) granules formed at sites of stalled mRNA translation (8,9). Ataxin-2 has also been shown to promote the assembly of neuronal RNP granules necessary for long-term memory formation (10). It is hypothesized that the expanded polyQ repeats in mutant ataxin-2 promote aberrant protein aggregation and degeneration in Purkinje neurons. Indeed, ataxin-2 has been shown to interact with TDP43, another RBP that is frequently associated with pathological aggregates and inclusion bodies in ALS and frontotemporal dementia (FTD) (3,11-14). It is currently unclear if mutant ataxin-2 drives neurodegeneration through toxic gain-of-function or loss of physiological function, and more research is needed in this area (15). However, targeting ataxin-2 therapeutically has shown initial promise, as antisense oligonucleotides against ataxin-2 improve motor function in SCA2 mouse models and increase survival in ALS mouse models (16,17).