| Property | Value | [1]
|----------|-------| [2]
| Protein Name | Ataxin-8 | [3]
| Aliases | SCA8 polyglutamine protein | [4]
| Gene | ATXN8 |
| UniProt ID | Q156A1 |
| Molecular Weight | Variable (~10-15 kDa, depending on repeat length) |
| Protein Family | Polyglutamine disease protein |
| Subcellular Localization | Nucleus (intranuclear inclusions) |
| Post-translational Modifications | Not well characterized |
Ataxin-8 is a protein encoded by the ATXN8 gene. This page describes its structure, normal nervous system function, role in neurodegenerative disease, and potential as a therapeutic target.
Ataxin-8 is a small protein encoded by the ATXN8 gene on the sense (CAG) strand of the bidirectionally transcribed SCA8 locus. Unlike most polyglutamine disease proteins (e.g., Huntingtin, Ataxin-1, Ataxin-3), Ataxin-8 lacks well-defined functional domains outside the polyglutamine tract.
Structural features:
| Protein | Gene | Normal Repeat | Pathogenic Repeat | Key Domains |
|---|---|---|---|---|
| Ataxin-8 | ATXN8 | 15-50 | 80-250 | PolyQ only |
| Huntingtin | HTT | 6-35 | 36-120+ | HEAT repeats |
| Ataxin-1 | ATXN1 | 6-44 | 39-82 | AXH domain |
| Ataxin-3 | ATXN3 | 12-44 | 55-87 | Josephin domain |
| Ataxin-7 | ATXN7 | 4-35 | 37-306 | SCA7 domain |
| Androgen receptor | AR | 9-36 | 38-62 | Steroid binding |
| Atrophin-1 | ATN1 | 7-34 | 49-88 | Transcriptional repressor |
Ataxin-8 contributes to SCA8 pathogenesis through multiple mechanisms, forming part of the "triple toxicity" model unique to this disease:
In addition to the canonical polyQ Ataxin-8 protein, the expanded CAG/CTG repeat undergoes repeat-associated non-AUG (RAN) translation in all three reading frames:
These RAN translation products:
Purkinje cells are preferentially affected in SCA8 due to:
| Strategy | Target | Rationale | Status |
|---|---|---|---|
| Antisense oligonucleotides | ATXN8 mRNA | Reduce toxic polyQ protein production | Preclinical |
| PolyQ aggregation inhibitors | Ataxin-8 protein | Prevent inclusion formation | Early research |
| Autophagy enhancers | Aggregated Ataxin-8 | Promote clearance of polyQ aggregates | Preclinical |
| RAN translation blockers | Repeat RNA | Prevent toxic polyS/polyA production | Early research |
| CRISPR repeat contraction | ATXN8 gene | Shorten the pathogenic repeat | Proof-of-concept |
Koob et al. An untranslated CTG expansion causes a novel form of spinocerebellar ataxia (SCA8) (1999). 1999. ↩︎
Banez-Coronel et al. RAN translation in Huntington disease (2015). 2015. ↩︎
Paulson et al. Polyglutamine spinocerebellar ataxias — from genes to potential treatments (2017). 2017. ↩︎
He et al. Targeted deletion of a single Sca8 ataxia locus allele in mice causes abnormal gait, progressive loss of motor coordination, and Purkinje cell dendritic deficits (2006). 2006. ↩︎