|
Spinocerebellar Ataxia Type 1
|
1.000 |
Biomarker
|
disease |
BEFREE |
Spinocerebellar ataxia type 1 (SCA1) is caused by the ataxin-1 protein (ATXN1) with an abnormally expanded polyglutamine tract and is characterized by progressive neurodegeneration.
|
27140210 |
2016 |
|
Spinocerebellar Ataxia Type 1
|
1.000 |
Biomarker
|
disease |
BEFREE |
These findings indicate that HSF1 is a key molecule in the regulation of the protein homeostasis of the polyQ-expanded mutant ATXN1 and that Hsp90 has potential as a novel therapeutic target in patients with SCA1.
|
27058144 |
2016 |
|
Spinocerebellar Ataxia Type 1
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Overall, the survival of mutation carriers through reproductive age, unaltered fertility rates, low childhood mortality in SCA1-affected families, and intergenerational transmission of increasing numbers of CAG repeats in the ATXN1 gene indicate that SCA1 in the Sakha population will be maintained at high prevalence levels.
|
27106293 |
2016 |
|
Spinocerebellar Ataxia Type 1
|
1.000 |
Biomarker
|
disease |
BEFREE |
Spinocerebellar ataxia type 1 (SCA1) is a dominantly inherited neurodegenerative disease of the cerebellum caused by a polyglutamine-repeat expansion in the protein ATXN1.
|
25255716 |
2015 |
|
Spinocerebellar Ataxia Type 1
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Mutant ataxin-1 (Atxn1), which causes spinocerebellar ataxia type 1 (SCA1), binds to and impairs the function of high-mobility group box 1 (HMGB1), a crucial nuclear protein that regulates DNA architectural changes essential for DNA damage repair and transcription.
|
25510912 |
2015 |
|
Spinocerebellar Ataxia Type 1
|
1.000 |
Biomarker
|
disease |
BEFREE |
Breeding Pum1(+/-) mice to SCA1 mice (Atxn1(154Q/+)) exacerbated disease progression, whereas breeding them to Atxn1(+/-) mice normalized Ataxin1 levels and largely rescued the Pum1(+/-) phenotype.
|
25768905 |
2015 |
|
Spinocerebellar Ataxia Type 1
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
We have discovered that astrocytes and microglia are activated very early in SCA1 pathogenesis even when mutant ATXN1 expression was limited to Purkinje neurons.
|
25595967 |
2015 |
|
Spinocerebellar Ataxia Type 1
|
1.000 |
Biomarker
|
disease |
GENOMICS_ENGLAND |
Genome sequencing identifies major causes of severe intellectual disability.
|
24896178 |
2014 |
|
Spinocerebellar Ataxia Type 1
|
1.000 |
Biomarker
|
disease |
BEFREE |
Because ATXN1 binds HDAC3, a Class I histone deacetylase (HDAC) that we have found to be required for ATXN1-induced transcriptional repression, we tested whether genetically depleting HDAC3 improves the phenotype of the SCA1 knock-in mouse (SCA1(154Q/2Q)), the most physiologically relevant model of SCA1.
|
24594842 |
2014 |
|
Spinocerebellar Ataxia Type 1
|
1.000 |
Biomarker
|
disease |
BEFREE |
This misfolded ATXN1 causes severe Purkinje cell (PC) loss and cerebellar ataxia in both humans and mice with the SCA1 disease.
|
24930030 |
2014 |
|
Spinocerebellar Ataxia Type 1
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
PolyQ (polyglutamine) diseases such as HD (Huntington's disease) or SCA1 (spinocerebellar ataxia type 1) are neurodegenerative disorders caused by abnormally elongated polyQ tracts in human proteins.
|
25131594 |
2014 |
|
Spinocerebellar Ataxia Type 1
|
1.000 |
Biomarker
|
disease |
BEFREE |
We discuss the paradigmatic example of ataxin-1 (Atx1), the protein responsible for neurodegenerative spinocerebellar ataxia type 1 (SCA1).
|
24636457 |
2014 |
|
Spinocerebellar Ataxia Type 1
|
1.000 |
Biomarker
|
disease |
BEFREE |
This review outlines different types of posttranslational modifications in ATXN1 and discusses their potential regulatory mechanisms and effects on SCA1 pathogenesis.
|
24752589 |
2014 |
|
Spinocerebellar Ataxia Type 1
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
In this study, we performed a systematic in vivo screen of all available Drosophila melanogaster homolog DNA repair genes, and we tested the effect of their overexpression on lifespan and developmental viability in Spinocerebellar Ataxia Type 1 (SCA1) Drosophila models expressing human mutant Ataxin-1 (Atxn1).
|
24179173 |
2014 |
|
Spinocerebellar Ataxia Type 1
|
1.000 |
Biomarker
|
disease |
BEFREE |
These data suggest that delivery of AAVs encoding RNAi sequences against ataxin-1, to DCN alone, may be sufficient for SCA1 therapy.
|
24419082 |
2014 |
|
Spinocerebellar Ataxia Type 1
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Spinocerebellar ataxia type 1 (SCA1) is a late onset autosomal dominant cerebellar ataxia, caused by CAG triplet repeat expansion in the ATXN1 gene.
|
25344417 |
2014 |
|
Spinocerebellar Ataxia Type 1
|
1.000 |
AlteredExpression
|
disease |
BEFREE |
Importantly, pharmacological inhibitors of components of this pathway also decrease ATXN1 levels, suggesting that these components represent new therapeutic targets in mitigating SCA1.
|
23719381 |
2013 |
|
Spinocerebellar Ataxia Type 1
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
In the case of the polyQ disease spinocerebellar ataxia type-1 (SCA1), interacting proteins with CC domains further enhance aggregation and toxicity of mutant ataxin-1 (ATXN1).
|
23483542 |
2013 |
|
Spinocerebellar Ataxia Type 1
|
1.000 |
Biomarker
|
disease |
BEFREE |
Recent studies suggest that understanding the normal function of ATXN1 in cellular processes is essential to decipher the pathogenesis mechanisms in spinocerebellar ataxia type 1.
|
23760502 |
2013 |
|
Spinocerebellar Ataxia Type 1
|
1.000 |
Biomarker
|
disease |
BEFREE |
Our results point to dysregulation of this newly assigned function of ataxin-1 in SCA1 uncovering new potential targets for therapy.
|
23630944 |
2013 |
|
Spinocerebellar Ataxia Type 1
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Clinical depression was evidenced in 68.4% of SCA1 and 75% non SCA-1 patients.
|
23634774 |
2013 |
|
Spinocerebellar Ataxia Type 1
|
1.000 |
Biomarker
|
disease |
BEFREE |
The nanoparticles were tested to deliver a functional siRNA against the Ataxin-1 gene in an in-vitro established model of a ND Spinocerebellar ataxia (SCA1) over-expressing ataxin protein.
|
23140978 |
2013 |
|
Spinocerebellar Ataxia Type 1
|
1.000 |
GeneticVariation
|
disease |
BEFREE |
Here, we compared the protective effects of overexpressing ataxin-1-like using recombinant AAVs, or reducing expression of mutant ataxin-1 using virally delivered RNA interference (RNAi), in a transgenic mouse model of SCA1.
|
23583610 |
2013 |
|
Spinocerebellar Ataxia Type 1
|
1.000 |
Biomarker
|
disease |
BEFREE |
Specifically, we show that NLK, a serine/threonine kinase that interacts with ATXN1, modulates disease phenotypes of polyglutamine-expanded ATXN1 in a Drosophila model of SCA1.
|
23719801 |
2013 |
|
Spinocerebellar Ataxia Type 1
|
1.000 |
Biomarker
|
disease |
BEFREE |
Previous studies indicate that while transgenic mice with ATXN1[30Q]-D776-induced disease share pathological features caused by ATXN1[82Q] having an expanded polyglutamine tract, they fail to manifest the age-related progressive neurodegeneration seen in spinocerebellar ataxia type 1.
|
23536093 |
2013 |