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Rethinking ALS: the FUS about TDP-43. Paper-13676809.
There were no mutations in GRN or TARDBP. Paper-13534024.
TDP43 depletion rescues aberrant CFTR exon 9 skipping. Paper-11381616.
These inclusions were also positive for p62 but not for TDP-43. Paper-12517164.
ATXN2 and TDP-43 associate in a complex that depends on RNA. Paper-15374030.
TDP-43 inclusions do not protect motor neurons from sporadic ALS. Paper-12884488.
Regulation of TDP-43 aggregation by phosphorylation and p62/ SQSTM1. Paper-15587516.
The pathology of DNTC included TDP-43 and aSyn pathology with high frequency. Paper-15626684.
Seven novel mutations (three in SOD1, two in TARDBP, two in FUS) were found. Paper-15315816.
FUS, TARDBP, and SOD1 mutations in a Taiwanese cohort with familial ALS. Paper-15209604.
Among them, T137R SOD1, G138E SOD1, H517D FUS, and N378D TARDBP were novel. Paper-15209604.
Lack of TAR-DNA binding protein-43 ( TDP-43) pathology in human prion diseases. Paper-13085196.
Mislocalization of TDP-43 in the G93A mutant SOD1 transgenic mouse model of ALS. Paper-13773228.
TDP-43 and FUS in amyotrophic lateral sclerosis and frontotemporal dementia. Paper-15401986.
Patients were screened for mutations in the progranulin ( GRN) and TDP-43 ( TARDBP) genes. Paper-13534024.
Mutations in SOD1, FUS, and TARDBP account for 20%, 13.3%, and 20% of FALS, respectively. Paper-15209604.
TDP-43 in the ubiquitin pathology of frontotemporal dementia with VCP gene mutations. Paper-13099951.
Since IBMPFD brain has TDP-43 in UBIs, we looked for TDP-43 inclusions in IBMPFD muscle. Paper-12948738.
Our results suggest a molecular link between reduced ADAR2 activity and TDP-43 pathology. Paper-15199505.
Here we investigated the influence of TDP-43 and its target HDAC6 on neurite outgrowth. Paper-16215636.
In IBMPFD muscle, TDP-43 is additionally present as large inclusions within UBIs in muscle cytoplasm. Paper-12948738.
Nuclear factor TDP-43 and SR proteins promote in vitro and in vivo CFTR exon 9 skipping. Paper-8827415.
Re-transfection with TDP-43 as well as HDAC6 rescued retinoic acid-induced neurite outgrowth. Paper-16215636.
Immunoblot analysis failed to recognize hyperphosphorylated TDP-43 at ~23 kDa in two MJD cases examined. Paper-13970962.
TDP-43 knockdown impairs neurite outgrowth dependent on its target histone deacetylase 6. Paper-16215636.
Histone deacetylase 6 ( HDAC6) is an established target of the RNA- binding protein TDP-43. Paper-16215636.
Here we investigate TDP-43 pathology in transgenic mice expressing the G93A mutant form of SOD1. Paper-13773228.
Here, we show that the presenilin-binding protein ubiquilin 1 ( UBQLN) plays a role in TDP-43 aggregation. Paper-13665124.
Moreover, TDP-43 bound specifically to HDAC6 mRNA arguing for a direct functional interaction. Paper-14199299.
Knockdown of transactive response DNA-binding protein ( TDP-43) downregulates histone deacetylase 6. Paper-14199299.
The control of Cdk6 expression mediated by TDP-43 involves GT repeats in the target gene sequence. Paper-14293770.
The most consistent findings are VCP, ubiquitin and TAR DNA-binding protein 43 ( TDP-43) positive inclusions. Paper-13750961.
TDP-43 pathology in sporadic ALS occurs in motor neurons lacking the RNA editing enzyme ADAR2. Paper-15199505.
Increased neuronal Rab5 immunoreactive endosomes do not colocalize with TDP-43 in motor neuron disease. Paper-15364825.
Over-expression of p62/ SQSTM1 reduces TDP-43 aggregation in an autophagy and proteasome-dependent manner. Paper-15587516.
Furthermore, TDP-43 aggregates colocalize with markers of autophagy and the adaptor protein p62/ SQSTM1. Paper-15587516.
Anterior horn cells with abnormal TDP-43 immunoreactivities show fragmentation of the Golgi apparatus in ALS. Paper-14419946.
In IBMPFD and sIBM muscle, TDP-43 migrated with an additional band on immunoblot similar to that reported in FTD-U brains. Paper-12948738.
Nonetheless, TDP-43 and FUS are promising candidates for the development of novel biomarker assays and targeted therapies. Paper-15401986.
Overexpression of SIGMAR1 shunted TDP-43 and FUS from the nucleus to the cytoplasm by 2.3-fold and 5.2-fold, respectively. Paper-15442506.
Here we report the 1.65 A crystal structure of the C-terminal RRM2 domain of TDP-43 in complex with a single-stranded DNA. Paper-13704172.
Affected brain and muscle tissue in IBMPFD have ubiquitinated and TAR DNA binding protein-43 ( TDP-43) inclusions. Paper-16211295.
VCP mutations causing frontotemporal lobar degeneration disrupt localization of TDP-43 and induce cell death. Paper-13735997.
We herein investigated the relationship between TDP-43 immunoreactivities and fragmentation of the Golgi apparatus ( GA). Paper-14419946.
TDP-43 mediates degeneration in a novel Drosophila model of disease caused by mutations in VCP/ p97. Paper-15144004.
ALS-associated mutations in TDP-43 increase its stability and promote TDP-43 complexes with FUS/ TLS. Paper-15321104.
MG132 enhances neurite outgrowth in neurons overexpressing mutant TAR DNA-binding protein-43 via increase of HO-1. Paper-16009905.
Here we show that TDP-43 and FUS/ TLS directly interact to form a complex at endogenous expression levels in mammalian cells. Paper-15406272.
In this study, we identified 29 phosphorylation sites on recombinant TDP-43 that are phosphorylated by casein kinase-1 ( CK1). Paper-13702393.
A fraction of TDP-43 is shown to be complexed with FUS/ TLS, an interaction substantially enhanced by TDP-43 mutants. Paper-15321104.
TAR DNA-binding protein-43 in amyotrophic lateral sclerosis, frontotemporal lobar degeneration, and Alzheimer disease. Paper-12884492.
In conclusion, loss of functional TDP-43 causes HDAC6 downregulation and might thereby contribute to pathogenesis. Paper-14199299.
RESULTS: 31 pathogenic missense mutations were found in 36 patients (20 SOD1, 1 ANG, 1 VAPB, 7 TARDBP and 7 FUS). Paper-15315816.
Common variation in the miR-659 binding-site of GRN is a major risk factor for TDP43-positive frontotemporal dementia. Paper-14336551.
The major component of the ubiquitinated inclusions of FTLD with VCP mutation is TDP-43 ( TAR DNA-binding protein of 43 kDa). Paper-13735997.
Potentiation of amyotrophic lateral sclerosis (ALS)-associated TDP-43 aggregation by the proteasome-targeting factor, ubiquilin 1. Paper-13665124.
Removal of TDP-43 in human cells significantly increases cyclin-dependent kinase 6 ( Cdk6) protein and transcript levels. Paper-14293770.
We used an adeno- associated virus ( AAV) vector for human TDP-43 expression targeted to the substantia nigra (SN) of rats. Paper-13696666.
Importantly, in vivo validation in TDP-43 knockout Drosophila melanogaster confirmed the specific downregulation of HDAC6. Paper-14199299.
Pathological TDP-43 is abnormally phosphorylated, ubiquitinated, and cleaved to generate carboxy-terminal fragments in affected brain regions. Paper-13439928.
These studies suggest motor neuron degeneration in the mutant SOD1 transgenic mice is associated with TDP-43 histopathology. Paper-13773228.
BACKGROUND: Mutations in SOD1, ANG, VAPB, TARDBP and FUS genes have been identified in amyotrophic lateral sclerosis (ALS). Paper-15315816.
How mutant TDP-43 reduces expression of HO-1 and prevents sulforaphane from activating Nrf2 signaling remains to be investigated. Paper-15334229.
HDAC6 levels were restored by re-expression of TDP-43, dependent on RNA binding and the C-terminal protein interaction domains. Paper-14199299.
SOD1, ANG, VAPB, TARDBP, and FUS mutations in familial amyotrophic lateral sclerosis: genotype-phenotype correlations. Paper-15315816.
As a result, we confirmed the high frequency of neuronal cytoplasmic accumulation of aSyn (80%) and phosphorylated TDP-43 (90%) in DNTC cases. Paper-15626684.
TDP-43 regulates retinoblastoma protein phosphorylation through the repression of cyclin-dependent kinase 6 expression. Paper-14293770.
Overexpression of UBQLN recruited TDP-43 to detergent-resistant cytoplasmic aggregates that colocalized with the autophagosomal marker, LC3. Paper-13665124.
In spinal cord neurons of ALS patients, ATXN2 is abnormally localized; likewise, TDP-43 shows mislocalization in spinocerebellar ataxia type 2. Paper-15374030.
Here, we analyzed the occurrence of TDP-43 immunostaining in Huntington disease, which is characterized by inclusions containing mutated huntingtin. Paper-13478099.
Furthermore, the area-portion of Rab5 immunoreactivity correlated well with the intracellular accumulation of ubiquitin, p62 and (phosphorylated) TDP-43. Paper-15364825.
Brains of SIGMAR1 mutation carriers displayed a unique pathology with cytoplasmic inclusions immunopositive for either TDP-43 or FUS but not Sigma-1. Paper-15442506.
The neurons were divided into subtypes according to differences in TDP-43 immunoreactivities, and we examined the morphological changes of GA in each type. Paper-14419946.
Significant correlations between immunoreactivity for TDP-43 and p62 were observed, particularly in p-FTLD-MND (Pearson correlation coefficient, 0.976). Paper-12884493.
In contrast, chromosome 3-linked dementia, FTLD-U with chromatin modifying protein 2B ( CHMP2B) mutation, has ub-ir, TDP-43-negative inclusions. Paper-12901401.
By post-injury day 42, no cytosolic TDP-43-positive neurons remained in NFL(-/-) mice, suggesting that they had undergone apoptotic cell death. Paper-14013430.
TDP-43 and FUS/ TLS have striking structural and functional similarities, implicating alterations in RNA processing as a key event in ALS pathogenesis. Paper-13676809.
Thus, TDP-43 is the newest member of the growing list of neurodegenerative proteinopathies, but unique in that it lacks features of brain amyloidosis. Paper-13439928.
TDP-43 C-terminal fragments were excluded from large molecular mass TDP-43 ribonucleoprotein complexes but retained FUS/ TLS binding activity. Paper-15406272.
Four ALS-associated alleles of TDP-43 also coaggregated with UBQLN, and the extent of aggregation correlated with in vitro UBQLN binding affinity. Paper-13665124.
The identification of MAPT and GRN defects and the discovery of the TDP-43 protein in FTD have led to the classification of pathologic and genetic subtypes. Paper-12957709.
Our data for the first time identifies UBAP1 as a genetic risk factor for FTLD and suggests a mechanistic relationship between this protein and TDP-43. Paper-13665818.
Colocalization of phospho- TDP-43 and phospho-tau was observed only in part of neuronal cytoplasmic inclusions, grain-like structures and NFT-like structures. Paper-13588188.
Together, our results show that degeneration associated with VCP mutations is mediated in part by toxic gain of function of TDP-43 in the cytoplasm. Paper-15144004.
Indeed, HDAC6-dependent reduction of cellular aggregate formation and increased cytotoxicity of polyQ-expanded ataxin-3 were found in TDP-43 silenced cells. Paper-14199299.
Our findings suggest that UBQLN is a polyubiquitin- TDP-43 cochaperone that mediates the autophagosomal delivery and/or proteasome targeting of TDP-43 aggregates. Paper-13665124.
Amyotrophic lateral sclerosis-associated proteins TDP-43 and FUS/ TLS function in a common biochemical complex to co-regulate HDAC6 mRNA. Paper-15406272.
Furthermore, we determined that a pathogenic mutation in TDP-43 promotes redistribution to the cytoplasm and enhances the genetic interaction with VCP. Paper-15144004.
A PTBP2 consensus RNA binding motif is enriched in the TDP-43 RIP-seq library, suggesting that PTBP2 may co-regulate TDP-43 RNA targets. Paper-15611524.
All of the neurons in Type A showed normal GA profiles, however, almost all of the neurons with abnormal TDP-43 immunoreactivities (Type B-D) showed GA fragmentation. Paper-14419946.
Nuclear factor TDP-43 binds to the polymorphic TG repeats in CFTR intron 8 and causes skipping of exon 9: a functional link with disease penetrance. Paper-10280636.
Other FTLD-U entities with TDP-43 proteinopathy include FTLD-U with valosin-containing protein ( VCP) gene mutation and FTLD with MND linked to chromosome 9p. Paper-13688226.
CONCLUSIONS: TDP-43 deficiency leads to impairment of neurite growth in an HDAC6-dependent manner, thereby contributing to neurodegenerative events in TDP-43 diseases. Paper-16215636.
Other FTLD-U entities with TDP-43 proteinopathy include: FTLD-U with valosin-containing protein ( VCP) gene mutation and FTLD with ALS linked to chromosome 9p. Paper-12901401.
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. Paper-15374030.
Enduring involvement of tau, beta-amyloid, alpha-synuclein, ubiquitin and TDP-43 pathology in the amyotrophic lateral sclerosis/parkinsonism-dementia complex of Guam (ALS/PDC). Paper-14476349.
Antisense inhibition of endogenous TDP-43 expression results in increased inclusion of exon 9, providing a new therapeutic target to correct aberrant splicing of exon 9 in CF patients. Paper-8827415.
In addition, we identified a case of familial FTLD that demonstrated colocalisation of UBAP1 and TDP-43 in the neuronal cytoplasmic inclusions in the brain of this individual. Paper-13665818.
However, emerging research has demonstrated that mutations and pathology associated with the TDP-43 gene and protein may be more common than SOD1 mutations in familial and sporadic ALS. Paper-13637777.
Mutations in the progranulin gene ( GRN) are an important cause of frontotemporal lobar degeneration ( FTLD) with ubiquitin and TAR DNA-binding protein 43 (TDP43)-positive pathology. Paper-13700348.
CONCLUSIONS: These data do not support a role for TDP-43 in prion disease pathogenesis and argue that TDP-43 inclusions define a distinct group of neurodegenerative disorders. Paper-13085196.
Here we show that ataxin 2 ( ATXN2), a polyglutamine (polyQ) protein mutated in spinocerebellar ataxia type 2, is a potent modifier of TDP-43 toxicity in animal and cellular models. Paper-15374030.
Our findings indicate that G93A mutant SOD1 transgenic mice recapitulate some key pathological, but not all biochemical hallmarks, of TDP-43 pathology previously observed in human ALS. Paper-13773228.
This study shows that TDP-43-positive inclusions were distributed throughout the subcortical white matter except for the occipital lobe in the FTLD-MND brain, but not in the ALS brain. Paper-12884493.
The authors analyzed these genes, including SOD1, FUS, VAPB, ANG, TDP-43, FIG4, and CHMP2B, in a cohort of 15 index patients of Han Chinese descent with adult-onset FALS. Paper-15209604.
All ADAR2-negative neurons had cytoplasmic inclusions that were immunoreactive to phosphorylated TDP-43, but lacked non-phosphorylated TDP-43 in the nucleus. Paper-15199505.
TDP-43 and FUS/ TLS associated with HDAC6 mRNA in intact cells and in vitro, and competition experiments suggested that the proteins occupy overlapping binding sites. Paper-15406272.
Whether these abnormal TDP-43 features are present in patients with SOD1-related familial ALS (fALS), or in mutant SOD1 over-expressing transgenic mouse models of ALS remains controversial. Paper-13773228.
No abnormal TDP-43 inclusions were identified in any type of prion disease case, and TDP-43 did not co-localize with ubiquitin-positive PrP plaques or with diffuse PrP aggregates. Paper-13085196.
However, sulforaphane could upregulate the expression of HO-1 and NAD(P)H/quinone oxidoreductase-1 ( NQO-1) in cells transfected with the empty vector and the wild-type TDP-43. Paper-15334229.
In contrast to previous reports we observe redistribution of TDP-43 to the cytoplasm of motor neurons in mutant SOD1 transgenic mice, but this is seen only in mice having advanced disease. Paper-13773228.
Seven different mutations in eight patients, including three in SOD1 (G85R, T137R, and G138E), two in exon 15 of FUS (H517D and R521H), and two in exon 6 of TARDBP (M337V and N378D) were identified. Paper-15209604.
These inclusions were also visualized with antibodies against phosphoserines 409 and 410 of TDP-43, and ubiquitin, but were not recognized by antibody against expanded polyglutamine stretches or ataxin-3. Paper-13970962.
In contrast, the mutant forms of FUS/ TLS accumulated in the cytoplasm of neurons, a pathology that is similar to that of the gene TAR DNA-binding protein 43 ( TDP43), whose mutations also cause ALS. Paper-13643042.
We have previously shown in a human embryonic kidney cell line that TDP-43 knockdown significantly impairs the removal of a toxic, aggregating polyQ ataxin-3 fusion protein in an HDAC6-dependent manner. Paper-16215636.
Taken together, abnormal stability of mutant TDP-43 and its enhanced binding to normal FUS/ TLS imply a convergence of pathogenic pathways from mutant TDP-43 and FUS/ TLS in ALS. Paper-15321104.
MATERIAL AND METHODS: TDP-43, ubiquitin and PrP were analysed by immunohistochemistry and double-labelling immunofluorescence, in sporadic, acquired and inherited forms of human prion disease. Paper-13085196.
Biochemically, hyperphosphorylated and truncated TDP-43 was detectable in insoluble brain extracts from affected white matter regions in FTLD-U, similar to the biochemical signature observed in FTLD-U gray matter. Paper-13151655.
Thereby, histone deacetylase 6 ( HDAC6) downregulation was discovered on TDP-43 silencing and confirmed at the mRNA and protein level in human embryonic kidney HEK293E and neuronal SH-SY5Y cells. Paper-14199299.
Cytosolic TDP-43 expression following axotomy is associated with caspase 3 activation in NFL-/- mice: support for a role for TDP-43 in the physiological response to neuronal injury. Paper-14013430.
UBQLN-dependent aggregation required the UBQLN UBA domain, was mediated by non-overlapping regions of TDP-43, and was abrogated by a mutation in UBQLN previously linked to Alzheimer disease. Paper-13665124.
To determine whether the ubiquitin pathology associated with mutations in VCP is characterized by the accumulation of TDP-43, we analyzed TDP-43 in the CNS pathology of five patients with VCP gene mutations. Paper-13099951.
TDP-43 positive structures included neuronal cytoplasmic inclusions, dystrophic neurites, glial cytoplasmic inclusions, grain-like dot-shaped structures, and neurofibrillary tangle (NFT)-like structures. Paper-13588188.
Cdk6 up-regulation in TDP-43-depleted cells is accompanied by an increase in phosphorylation of two of its major targets, the retinoblastoma protein pRb and pRb-related protein pRb2/p130. Paper-14293770.
The functional significance of TDP-43- FUS/ TLS complexes was established by showing that RNAi silencing of either TDP-43 or FUS/ TLS reduced the expression of histone deacetylase ( HDAC) 6 mRNA. Paper-15406272.
Mutations in two genes with related functions were recently reported in patients with familial ALS: the FUS/ TLS gene at the ALS6 locus on chromosome 16 and the TARDBP gene at the ALS10 locus on chromosome 1. Paper-13705534.
TDP-43 interacted with UBQLN both in yeast and in vitro, and the carboxyl-terminal ubiquitin-associated domain of UBQLN was both necessary and sufficient for binding to polyubiquitylated forms of TDP-43. Paper-13665124.
However, the immunohistochemical findings strongly suggested that in MJD, in addition to the polyglutamine-dependent disease process, TDP-43-related pathogenesis is associated with degeneration and death of the lower motor neurons. Paper-13970962.
However, HO-1 was down regulated in cells expressing the mutant TDP-43, and could not be restored by sulforaphane which is a known stimulator of Nrf2 and phase || detoxification enzyme, including HO-1. Paper-15334229.
It was recently found that dominant mutations in two related RNA-binding proteins, TDP-43 (43-kDa TAR DNA- binding domain protein) and FUS/ TLS (fused in sarcoma/translated in liposarcoma) cause a subset of ALS. Paper-15406272.
The convergent ALS phenotypes associated with TDP-43 and FUS/ TLS mutations are suggestive of a functional relationship; however, whether or not TDP-43 and FUS/ TLS operate in common biochemical pathways is not known. Paper-15406272.
These results further support that TDP-43 is involved in neurofilament mRNA metabolism and transport, and provide insight into the pathogenesis of motor neuron death in ALS in which NFL mRNA levels are selectively suppressed. Paper-14013430.
These findings suggest that whereas TDP-43 expression is normally upregulated transiently following axotomy, in the absence of NFL this response is delayed and associated with caspase 3 activation and neuronal death. Paper-14013430.
BACKGROUND AND PURPOSE: Frontotemporal lobar degeneration ( FTLD) can be subdivided into those in which the abnormal protein is tau (FTLD-TAU), the TAR DNA binding protein 43 (FTLD-TDP) and the fused in sarcoma protein (FTLD- FUS). Paper-15174812.
We therefore aimed to determine whether there is TDP-43 pathology in human prion diseases, which are characterised by variable deposition of prion protein ( PrP) aggregates in the brain as amyloid plaques or more diffuse deposits. Paper-13085196.
Morphological nuclear defects and increased apoptosis upon TDP-43 loss are mediated via the pRb pathway because pRb-negative cells (Saos-2) do not undergo programmed cell death or nuclear shape deformation upon TDP-43 removal. Paper-14293770.
We tried to clarify the molecular basis of DNTC by immunohistochemically examining the appearance and distribution of accumulated alpha-synuclein ( aSyn) and TAR DNA-binding protein of 43kDa ( TDP-43) in the brains of 10 Japanese autopsy cases. Paper-15626684.
The presence of AHCs with preserved nuclear TDP-43 and a fragmented Golgi apparatus, which are unrecognizable in sporadic ALS, indicates that patients with the E4787G OPTN mutation would manifest Golgi fragmentation before loss of nuclear TDP-43. Paper-16081549.
Identification of TDP-43, but not VCP, within ubiquitin-positive inclusions supports the hypothesis that VCP gene mutations lead to a dominant negative loss or alteration of VCP function culminating in impaired degradation of TDP-43. Paper-13099951.
Loss-of-function mutations in progranulin ( GRN) cause ubiquitin- and TAR DNA-binding protein 43 (TDP-43)-positive frontotemporal dementia (FTLD-U), a progressive neurodegenerative disease affecting approximately 10% of early-onset dementia patients. Paper-14336551.
We applied optimised voxel based morphometry (VBM) to brain MRIs from autopsy proven cases of tau positive frontotemporal lobar degeneration (FTLD-T, n = 6), ubiquitin and TDP-43 positive/tau negative FTLD (FTLD-U, n = 8) and cognitively normal controls (n = 61). Paper-12545436.
However, compared to C57BL6 mice and mtSOD1(G93A) mice, NFL(-/-) mice exhibited late upregulation of cytosolic TDP-43 expression and persistent downregulation of neuronal PGRN expression accompanied by caspase 3 activation on post-injury day 28. Paper-14013430.
To elucidate the maturation process of TDP-43-positive neuronal inclusions, we immunohistochemically and immunoelectron-microscopically examined multiple areas from the brain and spinal cord from ten patients with amyotrophic lateral sclerosis (ALS) and 25 control subjects. Paper-12884491.
In all Huntington disease cases studied, TDP-43 was frequently colocalized with huntingtin in dystrophic neurites and various intracellular inclusions, but not in intranuclear inclusions; the latter were only stained with huntingtin and anti-ubiquitin antibodies. Paper-13478099.
The striking functional and structural similarities of TDP-43 and FUS, which are both DNA/RNA binding proteins, imply that abnormal RNA metabolism is a pivotal event, but the mechanisms leading to TDP-43 and FUS accumulation and the resulting neurodegeneration are currently unknown. Paper-15401986.
The combined findings demonstrate that TDP-43 and FUS/ TLS form a functional complex in intact cells and suggest that convergent ALS phenotypes associated with TDP-43 and FUS/ TLS mutations may reflect their participation in common biochemical processes. Paper-15406272.
These studies thus characterize the recognition between TDP-43 and nucleic acids and the mode of RRM2 self association, and provide molecular models for understanding the role of TDP-43 in cystic fibrosis and the neurodegenerative diseases related to TDP-43 proteinopathy. Paper-13704172.
This study defined the distribution and frequency of mutations of FALS in a Taiwanese Han Chinese population, which not only broadens the spectrum of the mutations causing FALS, but also further highlights the importance of FUS and TARDBP in the pathogenesis of amyotrophic lateral sclerosis (ALS). Paper-15209604.
TAR DNA binding protein ( TDP43), a highly conserved heterogeneous nuclear ribonucleoprotein, was found to down-regulate splicing of the exon 9 cystic fibrosis transmembrane conductance regulator ( CFTR) through specific binding to a UG-rich polymorphic region upstream of the 3' splice site. Paper-10788006.
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. Paper-15144004.
We immunohistochemically examined the expression of adenosine deaminase acting on RNA 2 ( ADAR2), the enzyme that specifically catalyzes GluR2 Q/ R site-editing, and the expression of phosphorylated and non-phosphorylated TDP-43 in the spinal motor neurons of patients with sporadic ALS. Paper-15199505.
The finding of ubiquitin- and p62-positive, TDP-43-negative cytoplasmic inclusions in the hippocampus and neocortex suggests reclassification of the neuropathology of FTD-3 as a unique subtype of frontotemporal lobar degeneration with ubiquitin-positive inclusions that are TDP-43-negative. Paper-12517164.
Although the age at autopsy increased by 4.5-5 years per decade, we identified no qualitative differences in pathological deposits with antibodies against tau, ubiquitin, A beta, alpha-synuclein and TDP-43, indicating that these more recently identified proteins have been involved in the neuropathogenesis over the past 6 decades. Paper-14476349.
We have performed axotomies in two different presymptomatic models of motor neuron degeneration, low molecular weight neurofilament knockout ( NFL(-/-)) mice and mutant SOD1(G93A) transgenic (mtSOD1(G93A)) mice aged 6 weeks, and observed TDP-43 and PGRN expression patterns in axotomized spinal motor neurons over 28 days. Paper-14013430.
Clinical comparison of SOD1, TARDBP, FUS and other familial ALS patients (with no mutation in the screened genes) revealed differences in site of onset (predominantly lower limbs for SOD1 and upper limbs for TARDBP mutations), age of onset (younger with FUS mutations), and in lifespan (shorter for FUS carriers). Paper-15315816.
These synonyms are used for gene TARDBP (TAR DNA binding protein): TDP-43, TDP43, TAR DNA-binding protein 43, ALS10.
These accession numbers are used for gene TARDBP: EF434182 (NCBI_GENBANK__AC), E2PU12 (UNIPROT__AC), CR611899 (NCBI_GENBANK__AC), A4GUK5 (UNIPROT__AC).
TARDBP is a homologue of TBPH (CG10327 gene product from transcript CG10327-RC) from Drosophila melanogaster.
TARDBP is a homologue of TARDBP (TAR DNA binding protein) from Pan troglodytes.
TARDBP is a homologue of TARDBP (TAR DNA binding protein) from Gallus gallus.
TARDBP is a homologue of Tardbp (TAR DNA binding protein) from Mus musculus.
TARDBP is a homologue of tardbp (TAR DNA binding protein) from Danio rerio.
TARDBP is a homologue of AgaP_AGAP003497 (AGAP003497-PA) from Anopheles gambiae str. PEST.
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