|
Muscular Dystrophy, Oculopharyngeal
|
0.900 |
CausalMutation
|
disease |
CLINVAR |
|
|
|
|
Muscular Dystrophy, Oculopharyngeal
|
0.900 |
AlteredExpression
|
disease |
BEFREE |
Although PABPN1 plays a critical role in the regulation of RNA processing, mutation of the gene encoding this ubiquitously expressed RNA binding protein causes a specific form of muscular dystrophy termed oculopharyngeal muscular dystrophy (OPMD).
|
28977530 |
2017 |
|
Muscular Dystrophy, Oculopharyngeal
|
0.900 |
AlteredExpression
|
disease |
BEFREE |
Whereas PABP2 is expressed ubiquitously, the clinical and pathological features of OPMD patients are restricted to the skeletal muscle.
|
11371506 |
2001 |
|
Muscular Dystrophy, Oculopharyngeal
|
0.900 |
AlteredExpression
|
disease |
BEFREE |
Thus, low levels of PABPN1 protein could predispose specific tissues to pathology in OPMD.
|
29939290 |
2018 |
|
Muscular Dystrophy, Oculopharyngeal
|
0.900 |
AlteredExpression
|
disease |
BEFREE |
We identified cytokine-related genes candidates from a transcriptome study in a mouse overexpressing exp PABPN1 Six cytokines were found to be consistently down-regulated in OPMD vastus lateralis muscles.
|
27506982 |
2016 |
|
Muscular Dystrophy, Oculopharyngeal
|
0.900 |
AlteredExpression
|
disease |
BEFREE |
Here we show that the treatment of a mouse model of OPMD with an adeno-associated virus-based gene therapy combining complete knockdown of endogenous PABPN1 and its replacement by a wild-type PABPN1 substantially reduces the amount of insoluble aggregates, decreases muscle fibrosis, reverts muscle strength to the level of healthy muscles and normalizes the muscle transcriptome.
|
28361972 |
2017 |
|
Muscular Dystrophy, Oculopharyngeal
|
0.900 |
AlteredExpression
|
disease |
BEFREE |
Among six anti-PABPN1 intrabodies expressed in muscle nuclei, we identify one as a strong suppressor of OPMD muscle degeneration in Drosophila, leading to nearly complete rescue.
|
19258344 |
2009 |
|
Muscular Dystrophy, Oculopharyngeal
|
0.900 |
AlteredExpression
|
disease |
LHGDN |
This raises the possibility that a compromise of the anti-apoptotic function of PABPN1 might contribute to the disease mechanism of OPMD.
|
18178579 |
2008 |
|
Muscle degeneration
|
0.050 |
AlteredExpression
|
disease |
BEFREE |
Among six anti-PABPN1 intrabodies expressed in muscle nuclei, we identify one as a strong suppressor of OPMD muscle degeneration in Drosophila, leading to nearly complete rescue.
|
19258344 |
2009 |
|
Muscle degeneration
|
0.050 |
AlteredExpression
|
disease |
BEFREE |
We evaluated whether transgenic mouse model of OPMD, by expressing expanded PABPN1, indeed causes mitochondrial abnormality associated with muscle degeneration.
|
30894671 |
2019 |
|
Amyotrophic Lateral Sclerosis
|
0.010 |
AlteredExpression
|
disease |
BEFREE |
Reduced levels of PABPN1 enhances the phenotypes in several cell culture and Drosophila models of ALS and results in the cytoplasmic mislocalization of TDP-43.
|
26130692 |
2015 |
|
Non-Small Cell Lung Carcinoma
|
0.010 |
AlteredExpression
|
disease |
BEFREE |
We established and evaluated the APA score by quantitative RT-PCR in 147 clinical specimens of non-small cell lung cancer and compared the results with the clinical outcomes and expression levels of APA-related genes, including PABPN1, CPEB1, E2F1 and proliferation markers (MKI67, TOP2A and MCM2).
|
24975429 |
2014 |
|
Muscular Dystrophy, Oculopharyngeal
|
0.900 |
Biomarker
|
disease |
BEFREE |
A short abnormal (GCN) triplet expansion in the polyA-binding protein nuclear 1 (PABPN1) gene leads to PABPN1-containing aggregates in the muscles of OPMD patients.
|
30649389 |
2019 |
|
Muscular Dystrophy, Oculopharyngeal
|
0.900 |
Biomarker
|
disease |
BEFREE |
In concurrence with severe muscle degeneration in OPMD, the decline in PABPN1 accelerated in OPMD and was specific to skeletal muscles.
|
23793615 |
2013 |
|
Muscular Dystrophy, Oculopharyngeal
|
0.900 |
Biomarker
|
disease |
BEFREE |
PABPN1 protein accumulation is regulated by the ubiquitin proteasome system, which is highly dysregulated in oculopharyngeal muscular dystrophy.
|
24486325 |
2014 |
|
Muscular Dystrophy, Oculopharyngeal
|
0.900 |
Biomarker
|
disease |
BEFREE |
OPMD is caused by a small expansion of a short polyalanine tract in the poly (A) binding protein nuclear 1 protein (PABPN1).
|
17110089 |
2007 |
|
Muscular Dystrophy, Oculopharyngeal
|
0.900 |
Biomarker
|
disease |
BEFREE |
The expression of trePABPN1 in both a mouse model of OPMD and human cells elicited broad induction of proximal CS usage, linked to binding to endogenous PABPN1 and its sequestration in nuclear aggregates.
|
22502866 |
2012 |
|
Muscular Dystrophy, Oculopharyngeal
|
0.900 |
Biomarker
|
disease |
BEFREE |
Here, we explored a pharmacological manipulation of a Wnt signaling pathway using lithium chloride (LiCl), a GSK-3β inhibitor, and observed the enhanced expression of β-catenin protein as well as the decreased cell death normally observed in an OPMD cell model of murine myoblast (C2C12) expressing the expanded and pathogenic form of the expPABPN1.
|
24091664 |
2013 |
|
Muscular Dystrophy, Oculopharyngeal
|
0.900 |
Biomarker
|
disease |
BEFREE |
These findings suggest that oligomerization of PABPN1 plays a crucial role in the formation of OPMD nuclear protein aggregation, while the expanded polyalanine stretch is necessary but not sufficient to induce OPMD protein aggregation, and that the nuclear protein aggregation might be toxic and cause cell death.
|
11689481 |
2001 |
|
Muscular Dystrophy, Oculopharyngeal
|
0.900 |
Biomarker
|
disease |
BEFREE |
Established PABPN1 intranuclear inclusions in OPMD muscle can be efficiently reversed by AAV-mediated knockdown and replacement of mutant expanded PABPN1.
|
31294444 |
2019 |
|
Muscular Dystrophy, Oculopharyngeal
|
0.900 |
Biomarker
|
disease |
BEFREE |
Recent studies have suggested that a loss of PABPN1 function could contribute to muscle pathology in OPMD.
|
28575395 |
2017 |
|
Muscular Dystrophy, Oculopharyngeal
|
0.900 |
Biomarker
|
disease |
BEFREE |
While the roles of PABPN1 in nuclear polyadenylation and regulation of alternative poly(A) site choice are established, the molecular mechanisms behind OPMD remain undetermined.
|
25816335 |
2015 |
|
Muscular Dystrophy, Oculopharyngeal
|
0.900 |
Biomarker
|
disease |
BEFREE |
As part of our effort to clone positionally the oculopharyngeal muscular dystrophy (OPMD) gene, we constructed a YAC contig, a cosmid contig, and an EcoRI restriction map of the OPMD candidate region.
|
9782086 |
1998 |
|
Muscular Dystrophy, Oculopharyngeal
|
0.900 |
Biomarker
|
disease |
BEFREE |
These include lamin A/C in autosomal dominant Emery-Dreifuss muscular dystrophy, SMN in spinal muscular atrophy, SIX5 in myotonic dystrophy, calpain3 in type 2A limb-girdle muscular dystrophy, PABP2 in oculopharyngeal dystrophy, androgen receptor in spinal and bulbar muscular atrophy and the ataxins in hereditary ataxias.
|
10838245 |
2000 |
|
Muscular Dystrophy, Oculopharyngeal
|
0.900 |
Biomarker
|
disease |
BEFREE |
Interestingly, knockdown of the PABPN1 by selective hhRzs in the C. elegans OPMD model significantly improved the motility of the PABPN1-13Ala worms.
|
30831428 |
2019 |