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TDP-43 Proteinopathies
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0.100 |
Biomarker
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disease |
BEFREE |
In the majority of nontauopathy disorders the recently identified TAR DNA-binding protein-43 (TDP-43) is found as the major inclusion protein (TDP-43 proteinopathies), and TDP-43 is also present in motor neuron inclusions of amyotrophic lateral sclerosis.
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17702495 |
2007 |
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TDP-43 Proteinopathies
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0.100 |
Biomarker
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disease |
BEFREE |
Thus, TDP-43 defines a novel class of neurodegenerative diseases called TDP-43 proteinopathies.
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17591968 |
2007 |
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TDP-43 Proteinopathies
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0.100 |
Biomarker
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disease |
BEFREE |
Morphologically distinct inclusion components may reflect the process of TDP-43 aggregation and interaction with other proteins: determining these latter may contribute towards understanding the heterogeneous pathogenesis of FTLD with TDP-43 proteinopathy.
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18974920 |
2008 |
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TDP-43 Proteinopathies
|
0.100 |
Biomarker
|
disease |
BEFREE |
The TAR DNA-binding protein 43 (TDP-43) has been identified as the major disease protein in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitin inclusions (FTLD-U), defining a novel class of neurodegenerative conditions: the TDP-43 proteinopathies.
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18802454 |
2008 |
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TDP-43 Proteinopathies
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0.100 |
Biomarker
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disease |
BEFREE |
The number of neurodegenerative diseases associated with pathological aggregates of transactivation response element (TAR)-DNA-binding protein 43 (TDP-43) has increased, leading to the new designation 'TDP-43 proteinopathy.'
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18549326 |
2008 |
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TDP-43 Proteinopathies
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0.100 |
Biomarker
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disease |
BEFREE |
The recent discovery of pathological TDP-43 in both amyotrophic lateral sclerosis and frontotemporal lobar degeneration with ubiquitinated inclusions confirms that these are closely related conditions within a new biochemical class of neurodegenerative disease, the TDP-43 proteinopathies.
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18989115 |
2008 |
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TDP-43 Proteinopathies
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0.100 |
Biomarker
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disease |
BEFREE |
The finding of pathogenic mutations in TARDBP implicates TDP-43 as an active mediator of neurodegeneration in TDP-43 proteinopathies, a class of disorder that includes ALS and FTLD-U.
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18396105 |
2008 |
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TDP-43 Proteinopathies
|
0.100 |
Biomarker
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disease |
BEFREE |
Our results suggest that intracellular localization of TDP-43 and proteasomal function may be involved in inclusion formation and neurodegeneration in TDP-43 proteinopathies.
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19111550 |
2009 |
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TDP-43 Proteinopathies
|
0.100 |
AlteredExpression
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disease |
BEFREE |
Here we have identified the specific cleavage site, Arg(208), of a pathological TDP-43 CTF purified from FTLD-U brains and show that the expression of this and other TDP-43 CTFs in cultured cells recapitulates key features of TDP-43 proteinopathy.
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19164285 |
2009 |
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TDP-43 Proteinopathies
|
0.100 |
GeneticVariation
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disease |
BEFREE |
In summary, TARDBP variants may result in clinically and neuropathologically heterogeneous phenotypes linked by a common molecular pathology called TDP-43 proteinopathy.
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19618195 |
2009 |
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TDP-43 Proteinopathies
|
0.100 |
GeneticVariation
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disease |
BEFREE |
The TDP-43 proteinopathy associated with CTE is similar to that found in frontotemporal lobar degeneration with TDP-43 inclusions, in that widespread regions of the brain are affected.
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20720505 |
2010 |
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TDP-43 Proteinopathies
|
0.100 |
Biomarker
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disease |
BEFREE |
This robust rat model also recapitulated features of TDP-43 proteinopathies including the formation of TDP-43 inclusions, cytoplasmic localization of phosphorylated TDP-43, and fragmentation of TDP-43 protein.
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20361056 |
2010 |
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TDP-43 Proteinopathies
|
0.100 |
Biomarker
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disease |
BEFREE |
Furthermore, these findings indicate that the TDP-43-ATXN2 interaction may be a promising target for therapeutic intervention in ALS and other TDP-43 proteinopathies.
|
20740007 |
2010 |
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TDP-43 Proteinopathies
|
0.100 |
Biomarker
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disease |
BEFREE |
We have developed a Caenorhabditis elegans model of TDP-43 proteinopathies to study the cellular, molecular, and genetic underpinnings of TDP-43-mediated neurotoxicity.
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21123567 |
2010 |
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TDP-43 Proteinopathies
|
0.100 |
Biomarker
|
disease |
BEFREE |
Here we demonstrate that VCP and TDP-43 interact genetically and that disease-causing mutations in VCP lead to redistribution of TDP-43 to the cytoplasm in vitro and in vivo, replicating the major pathology observed in IBMPFD and other TDP-43 proteinopathies.
|
20519548 |
2010 |
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TDP-43 Proteinopathies
|
0.100 |
GeneticVariation
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disease |
BEFREE |
Transgenic mouse lines expressing untagged mutant and wild type TDP-43 under the same promoter represent a powerful new model system for studying TDP-43 proteinopathies in vivo.
|
20621187 |
2010 |
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TDP-43 Proteinopathies
|
0.100 |
Biomarker
|
disease |
BEFREE |
These findings suggest that 15d-PGJ(2) is an endogenous modifier of TDP-43 protein in TDP-43 proteinopathy.
|
20083106 |
2010 |
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TDP-43 Proteinopathies
|
0.100 |
Biomarker
|
disease |
BEFREE |
The identification of TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis cases confirms its pathogenic role; but it is wild-type TDP-43 that is deposited in the vast majority of TDP-43 proteinopathies, implicating other unknown factors for its mislocalization and aggregation.
|
20472655 |
2010 |
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TDP-43 Proteinopathies
|
0.100 |
GeneticVariation
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disease |
BEFREE |
Prospective longitudinal clinical evaluation and retrospective medical record review, immunohistochemical identification of pathological TDP-43 in the central nervous system, and genotyping for gene alterations known to cause TDP-43 proteinopathies including the TDP-43 (TARDBP) and progranulin (GRN) genes.
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20937952 |
2010 |
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TDP-43 Proteinopathies
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0.100 |
Biomarker
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disease |
BEFREE |
The conservation of the regulatory pathways of functions and dysfunctions of Drosophila dTDP and mammalian TDP-43 also shows the feasibility of using the flies as a model system for studying the normal TDP-43 function and TDP-43 proteinopathies in the vertebrates including human.
|
21673800 |
2011 |
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TDP-43 Proteinopathies
|
0.100 |
Biomarker
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disease |
BEFREE |
In C. elegans, the neurotoxicity and the protein aggregation of TDP-43 were regulated by environmental temperature and heat shock transcriptional factor 1, indicating that a deficiency in protein quality control is a risk factor for TDP-43 proteinopathy.
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21355045 |
2011 |
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TDP-43 Proteinopathies
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0.100 |
AlteredExpression
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disease |
BEFREE |
In conclusion, our data show that TDP-43 expression in flies recapitulates several biochemical key features of human TDP-43 proteinopathies, including abnormal phosphorylation on a disease-specific site and processing of the protein.
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20951205 |
2011 |
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TDP-43 Proteinopathies
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0.100 |
Biomarker
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disease |
BEFREE |
Finally, we review current mouse models of TDP-43 and discuss their similarities and potential relevance to human TDP-43 proteinopathies including ALS and FTLD-TDP.
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21783422 |
2011 |
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TDP-43 Proteinopathies
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0.100 |
Biomarker
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disease |
BEFREE |
To explore the mechanistic details that result in aberrant accumulation of TDP-43 and to discover potential strategies for therapeutic intervention, we employed a yeast TDP-43 proteinopathy model system.
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21115123 |
2011 |
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TDP-43 Proteinopathies
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0.100 |
Biomarker
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disease |
BEFREE |
Our work also suggests that decreasing the abundance of neurotoxic TDP-43 species, enhancing degradation or clearance of such TDP-43 derivatives and blocking the spread of the disease phenotype may have therapeutic potential for TDP-43 proteinopathies.
|
21666678 |
2011 |