|
Amyotrophic Lateral Sclerosis
|
0.700 |
Biomarker
|
disease |
BEFREE |
Deletion of the ATXN2 ortholog, PBP1, reduces yeast TDP-43 toxicity, which led to identification of ATXN2 as an amyotrophic lateral sclerosis (ALS) risk factor and therapeutic target.
|
31390360 |
2019 |
|
Amyotrophic Lateral Sclerosis
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Intermediate-length ATXN2 CAG repeats are a risk factor for amyotrophic lateral sclerosis (ALS).
|
30342765 |
2019 |
|
Amyotrophic Lateral Sclerosis
|
0.700 |
Biomarker
|
disease |
BEFREE |
Association of ATXN2 intermediate-length CAG repeats with amyotrophic lateral sclerosis correlates with the distributions of normal CAG repeat alleles among individual ethnic populations.
|
30847648 |
2019 |
|
Amyotrophic Lateral Sclerosis
|
0.700 |
AlteredExpression
|
disease |
BEFREE |
Therefore, targeting the PTK2-TBK1-SQSTM1 axis may represent a novel therapeutic intervention for neurodegenerative diseases with TARDBP proteinopathies.<b>Abbreviations</b>: ALP: macroautophagy/autophagy lysosomal pathway; ALS: amyotrophic lateral sclerosis; ATXN2: ataxin 2; BafA1: bafilomycin A<sub>1</sub>; cCASP3: cleaved caspase 3; CSNK2: casein kinase 2; FTLD: frontotemporal lobar degeneration; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; OPTN: optineurin; PTK2/FAK: PTK2 protein tyrosine kinase 2; SQSTM1/p62: sequestosome 1; TARDBP/TDP-43: TAR DNA binding protein; TBK1: TANK binding kinase 1; ULK1: unc-51 like autophagy activating kinase 1; UPS: ubiquitin-proteasome system.
|
31690171 |
2019 |
|
Amyotrophic Lateral Sclerosis
|
0.700 |
Biomarker
|
disease |
BEFREE |
Furthermore, an oligogenic basis of ALS was observed in three sALS, with co-occurrence of intermediate-length repeat expansions in ATXN2 and a rare/novel variant in DCTN1 and SETX genes.
|
31432357 |
2019 |
|
Amyotrophic Lateral Sclerosis
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Intermediate repeat expansions at the Ataxin-2 locus (ATXN2) are a risk factor for ALS and influence the phenotype.
|
30342763 |
2019 |
|
Amyotrophic Lateral Sclerosis
|
0.700 |
Biomarker
|
disease |
BEFREE |
We performed genetic testing consisting of C9orf72 hexanucleotide expansion, ATXN2 polyglutamine (polyQ) expansion, and targeted next generation sequencing using the ONDRISeq, a gene panel consisting of 80 genes known to be associated with neurodegenerative diseases such as ALS, FTD, Alzheimer's disease, Parkinson's disease, and vascular cognitive impairment.
|
29080331 |
2018 |
|
Amyotrophic Lateral Sclerosis
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Studies on genetic aberrations among Indian amyotrophic lateral sclerosis (ALS) patients are limited to C9orf72 and ATXN2 repeat expansions and mutations in the SOD1 gene.
|
29895397 |
2018 |
|
Amyotrophic Lateral Sclerosis
|
0.700 |
Biomarker
|
disease |
BEFREE |
Our findings support the hypothesis that ATXN2 plays an important role in the pathogenesis of ALS also in the Brazilian population.
|
29934271 |
2018 |
|
Amyotrophic Lateral Sclerosis
|
0.700 |
Biomarker
|
disease |
BEFREE |
We identified Staufen1 (STAU1) as an interactor of ATXN2, and showed elevation in cells from SCA2 patients, amyotrophic lateral sclerosis (ALS) patients, and in SCA2 mouse models.
|
30194296 |
2018 |
|
Amyotrophic Lateral Sclerosis
|
0.700 |
Biomarker
|
disease |
BEFREE |
In addition, the phenotype of SCA2 expansions has been now extended to Parkinson disease and amyotrophic lateral sclerosis.
|
29462666 |
2018 |
|
Amyotrophic Lateral Sclerosis
|
0.700 |
Biomarker
|
disease |
BEFREE |
Human Ataxin-2 is implicated in the cause and progression of amyotrophic lateral sclerosis (ALS) and type 2 spinocerebellar ataxia (SCA-2).
|
29772202 |
2018 |
|
Amyotrophic Lateral Sclerosis
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
These findings support the notion that intermediate-length ATXN2 repeat expansions might be a risk factor in Korean patients with ALS.
|
29665996 |
2018 |
|
Amyotrophic Lateral Sclerosis
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Recent studies have identified the RNA-binding protein Ataxin-2 as a genetic determinant or risk factor for various diseases including spinocerebellar ataxia type II (SCA2) and amyotrophic lateral sclerosis (ALS), amongst others.
|
28587229 |
2017 |
|
Amyotrophic Lateral Sclerosis
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Long ATXN2 polyQ repeats (≥33Qs) were not present in any of the ALS patients or controls.
|
28527524 |
2017 |
|
Amyotrophic Lateral Sclerosis
|
0.700 |
Biomarker
|
disease |
BEFREE |
Recent findings linking ataxin-2 intermediate expansions to other neurodegenerative diseases such as amyotrophic lateral sclerosis have provided insights into the ataxin-2-related toxicity mechanism in neurodegenerative diseases and have raised new ethical challenges to molecular predictive diagnosis of SCA2.
|
28955296 |
2017 |
|
Amyotrophic Lateral Sclerosis
|
0.700 |
Biomarker
|
disease |
BEFREE |
Pathological developments leading to amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are associated with misbehavior of several key proteins, such as SOD1 (superoxide dismutase 1), TARDBP/TDP-43, FUS, C9orf72, and dipeptide repeat proteins generated as a result of the translation of the intronic hexanucleotide expansions in the C9orf72 gene, PFN1 (profilin 1), GLE1 (GLE1, RNA export mediator), PURA (purine rich element binding protein A), FLCN (folliculin), RBM45 (RNA binding motif protein 45), SS18L1/CREST, HNRNPA1 (heterogeneous nuclear ribonucleoprotein A1), HNRNPA2B1 (heterogeneous nuclear ribonucleoprotein A2/B1), ATXN2 (ataxin 2), MAPT (microtubule associated protein tau), and TIA1 (TIA1 cytotoxic granule associated RNA binding protein).
|
28980860 |
2017 |
|
Amyotrophic Lateral Sclerosis
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Intermediate interrupted ataxin 2 (ATXN2) alleles (27-33 CAG-repeats) increase the risk for amyotrophic lateral sclerosis and are reported as modifiers in chromosome 9 open reading frame 72 (C9orf72) carriers, rendering susceptibility to amyotrophic lateral sclerosis rather than frontotemporal lobar degeneration.
|
28124431 |
2017 |
|
Amyotrophic Lateral Sclerosis
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
A decrease in ataxin-2 suppresses TDP-43 toxicity in yeast and flies, and intermediate-length polyglutamine expansions in the ataxin-2 gene increase risk of ALS.
|
28405022 |
2017 |
|
Amyotrophic Lateral Sclerosis
|
0.700 |
Biomarker
|
disease |
BEFREE |
In contrast to trinucleotide repeat diseases, intermediate ATXN2 trinucleotide repeat expansion in ALS does not predict age of onset but does predict disease risk.
|
28017481 |
2017 |
|
Amyotrophic Lateral Sclerosis
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Risk factors that may be associated with ALS include: 1) genetic mutations, including the intermediate CAG repeat expansion in ATXN2; 2) previous exposure to heavy metals such as lead and mercury; 3) previous exposure to organic chemicals, such as pesticides and solvents; 4) history of electric shock; 5) history of physical trauma/injury (including head trauma/injury); 6) smoking (a weak risk factor for ALS in women); and 6) other risk factors, such as participating in professional sports, lower body mass index, lower educational attainment, or occupations requiring repetitive/strenuous work, military service, exposure to Beta-N-methylamino-l-alanin and viral infections.
|
27377857 |
2017 |
|
Amyotrophic Lateral Sclerosis
|
0.700 |
Biomarker
|
disease |
CTD_human |
Risk factors that may be associated with ALS include: 1) genetic mutations, including the intermediate CAG repeat expansion in ATXN2; 2) previous exposure to heavy metals such as lead and mercury; 3) previous exposure to organic chemicals, such as pesticides and solvents; 4) history of electric shock; 5) history of physical trauma/injury (including head trauma/injury); 6) smoking (a weak risk factor for ALS in women); and 6) other risk factors, such as participating in professional sports, lower body mass index, lower educational attainment, or occupations requiring repetitive/strenuous work, military service, exposure to Beta-N-methylamino-l-alanin and viral infections.
|
27377857 |
2017 |
|
Amyotrophic Lateral Sclerosis
|
0.700 |
Biomarker
|
disease |
BEFREE |
In addition to classic cerebellar and brainstem signs, however, SCA2 can also present as a parkinsonian syndrome or as amyotrophic lateral sclerosis.
|
27298447 |
2016 |
|
Amyotrophic Lateral Sclerosis
|
0.700 |
Biomarker
|
disease |
BEFREE |
Motor neurone disease/amyotrophic lateral sclerosis associated with intermediate-length CAG repeat expansions in Ataxin-2 does not have 1C2-positive polyglutamine inclusions.
|
26095883 |
2016 |
|
Amyotrophic Lateral Sclerosis
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
ATXN2-AS transcripts with normal and expanded CUG repeats are expressed in human postmortem SCA2 brains, human SCA2 fibroblasts, induced SCA2 pluripotent stem cells, SCA2 neural stem cells, and lymphoblastoid lines containing an expanded ATXN2 allele associated with ALS.
|
27531668 |
2016 |