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16 results for “TDP-43”
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Dual-targeting snRNA gene therapy rescues STMN2 and UNC13A splicing in TDP-43 proteinopathies.
bioRxiv : the preprint server for biology · 2025
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder caused by the selective deterioration of motor neurons in the central nervous system (CNS). A key driver of this pathogenesis is nuclear loss of ALS-associated protein TDP-43, leading to mis-splicing of TDP-43 …
PMID 41573891 DOI ↗
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Investigational eIF2B activator DNL343 modulates the integrated stress response in preclinical models of TDP-43 pathology and individuals with ALS in a randomized clinical trial.
Nature communications · 2025 · 16(1): 7690
Neuronal TDP-43 aggregates are a hallmark ALS pathology. The integrated stress response (ISR) occurs downstream of TDP-43 pathology and may promote neurodegeneration. Here we demonstrate that a CNS penetrant small molecule eIF2B activator inhibits the ISR in cellular models of …
PMID 40825784 DOI ↗
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Neuronal aging causes mislocalization of splicing proteins and unchecked cellular stress.
Nature neuroscience · 2025 · 28(6): 1174-1184
Aging is one of the most prominent risk factors for neurodegeneration, yet the molecular mechanisms underlying the deterioration of old neurons are mostly unknown. To efficiently study neurodegeneration in the context of aging, we transdifferentiated primary human fibroblasts from aged …
PMID 40456907 DOI ↗
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Inhibition of RNA splicing triggers CHMP7 nuclear entry, impacting TDP-43 function and leading to the onset of ALS cellular phenotypes.
Neuron · 2024 · 112(24): 4033-4047.e8
Amyotrophic lateral sclerosis (ALS) is linked to the reduction of certain nucleoporins in neurons. Increased nuclear localization of charged multivesicular body protein 7 (CHMP7), a protein involved in nuclear pore surveillance, has been identified as a key factor damaging nuclear …
PMID 39486415 DOI ↗
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High-sensitivity in situ capture of endogenous RNA-protein interactions in fixed cells and primary tissues.
Nature communications · 2024 · 15(1): 7067
RNA-binding proteins (RBPs) have pivotal functions in RNA metabolism, but current methods are limited in retrieving RBP-RNA interactions within endogenous biological contexts. Here, we develop INSCRIBE (IN situ Sensitive Capture of RNA-protein Interactions in Biological Environments), circumventing the challenges through …
PMID 39152130 DOI ↗
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Aberrant NOVA1 function disrupts alternative splicing in early stages of amyotrophic lateral sclerosis.
Acta neuropathologica · 2022 · 144(3): 413-435
Amyotrophic lateral sclerosis (ALS) is a fatal disease characterized by aberrant alternative splicing (AS). Nuclear loss and cytoplasmic accumulation of the splicing factor TDP-43 in motor neurons (MN) are hallmarks of ALS at late stages of the disease. However, it …
PMID 35778567 DOI ↗
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S-nitrosylated TDP-43 triggers aggregation, cell-to-cell spread, and neurotoxicity in hiPSCs and in vivo models of ALS/FTD.
Proceedings of the National Academy of Sciences of the United States of America · 2021 · 118(11)
Rare genetic mutations result in aggregation and spreading of cognate proteins in neurodegenerative disorders; however, in the absence of mutation (i.e., in the vast majority of "sporadic" cases), mechanisms for protein misfolding/aggregation remain largely unknown. Here, we show environmentally induced …
PMID 33692125 DOI ↗
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Regulation of RNA editing by RNA-binding proteins in human cells.
Communications biology · 2019 · 2: 19
Adenosine-to-inosine (A-to-I) editing, mediated by the ADAR enzymes, diversifies the transcriptome by altering RNA sequences. Recent studies reported global changes in RNA editing in disease and development. Such widespread editing variations necessitate an improved understanding of the regulatory mechanisms of …
PMID 30652130 DOI ↗
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Small-Molecule Modulation of TDP-43 Recruitment to Stress Granules Prevents Persistent TDP-43 Accumulation in ALS/FTD.
Neuron · 2019 · 103(5): 802-819.e11
Stress granules (SGs) form during cellular stress and are implicated in neurodegenerative diseases such as amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD). To yield insights into the role of SGs in pathophysiology, we performed a high-content screen to identify small …
PMID 31272829 DOI ↗
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Transcriptome-pathology correlation identifies interplay between TDP-43 and the expression of its kinase CK1E in sporadic ALS.
Acta neuropathologica · 2018 · 136(3): 405-423
Sporadic amyotrophic lateral sclerosis (sALS) is the most common form of ALS, however, the molecular mechanisms underlying cellular damage and motor neuron degeneration remain elusive. To identify molecular signatures of sALS we performed genome-wide expression profiling in laser capture microdissection-enriched …
PMID 29881994 DOI ↗
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Distinct and shared functions of ALS-associated proteins TDP-43, FUS and TAF15 revealed by multisystem analyses.
Nature communications · 2016 · 7: 12143
The RNA-binding protein (RBP) TAF15 is implicated in amyotrophic lateral sclerosis (ALS). To compare TAF15 function to that of two ALS-associated RBPs, FUS and TDP-43, we integrate CLIP-seq and RNA Bind-N-Seq technologies, and show that TAF15 binds to ∼4,900 RNAs …
PMID 27378374 DOI ↗
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Targeted degradation of sense and antisense C9orf72 RNA foci as therapy for ALS and frontotemporal degeneration.
Proceedings of the National Academy of Sciences of the United States of America · 2013 · 110(47): E4530-9
Expanded hexanucleotide repeats in the chromosome 9 open reading frame 72 (C9orf72) gene are the most common genetic cause of ALS and frontotemporal degeneration (FTD). Here, we identify nuclear RNA foci containing the hexanucleotide expansion (GGGGCC) in patient cells, including …
PMID 24170860 DOI ↗
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ALS-linked TDP-43 mutations produce aberrant RNA splicing and adult-onset motor neuron disease without aggregation or loss of nuclear TDP-43.
Proceedings of the National Academy of Sciences of the United States of America · 2013 · 110(8): E736-45
Transactivating response region DNA binding protein (TDP-43) is the major protein component of ubiquitinated inclusions found in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) with ubiquitinated inclusions. Two ALS-causing mutants (TDP-43(Q331K) and TDP-43(M337V)), but not wild-type human TDP-43, …
PMID 23382207 DOI ↗
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Divergent roles of ALS-linked proteins FUS/TLS and TDP-43 intersect in processing long pre-mRNAs.
Nature neuroscience · 2012 · 15(11): 1488-97
FUS/TLS (fused in sarcoma/translocated in liposarcoma) and TDP-43 are integrally involved in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. We found that FUS/TLS binds to RNAs from >5,500 genes in mouse and human brain, primarily through a GUGGU-binding motif. We …
PMID 23023293 DOI ↗
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Misregulated RNA processing in amyotrophic lateral sclerosis.
Brain research · 2012 · 1462: 3-15
Amyotrophic lateral sclerosis (ALS) research is undergoing an era of unprecedented discoveries with the identification of new genes as major genetic causes of this disease. These discoveries reinforce the genetic, clinical and pathological overlap between ALS and frontotemporal lobar degeneration …
PMID 22444279 DOI ↗
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Long pre-mRNA depletion and RNA missplicing contribute to neuronal vulnerability from loss of TDP-43.
Nature neuroscience · 2011 · 14(4): 459-68
We used cross-linking and immunoprecipitation coupled with high-throughput sequencing to identify binding sites in 6,304 genes as the brain RNA targets for TDP-43, an RNA binding protein that, when mutated, causes amyotrophic lateral sclerosis. Massively parallel sequencing and splicing-sensitive junction …
PMID 21358643 DOI ↗
Datasets 25+
Inhibition of RNA splicing triggers CHMP7 nuclear entry impacting TDP-43 function and leading to onset of ALS (eCLIP).
Homo sapiens · GPL24676
Inhibition of RNA splicing triggers CHMP7 nuclear entry impacting TDP-43 function and leading to onset of ALS
Homo sapiens · GPL24676
Inhibition of RNA splicing triggers CHMP7 nuclear entry impacting TDP-43 function and leading to onset of ALS (RNA-Seq).
Homo sapiens · Illumina
RNA-seq on K562 cells treated with an shRNA knockdown against TDP-43. (K562-set1b-shTDP43)
Homo sapiens
Premature polyadenylation-mediated loss of stathmin-2 is a hallmark of TDP-43-dependent neurodegeneration
Homo sapiens · GPL20301
Postmortem Cortex Samples Identify Distinct Molecular Subtypes of ALS: Retrotransposon Activation, Oxidative Stress, and Activated Glia [motor cortex]
Homo sapiens · GPL18573
ALS implicated protein TDP-43 sustains levels of STMN2 a mediator of motor neuron growth and repair
Homo sapiens · GPL11154
Loss of nuclear TDP-43 in ALS causes altered expression of splicing machinery and widespread dysregulation of RNA splicing in motor neurons
Mus musculus · GPL5188
Postmortem Cortex Samples Identify Distinct Molecular Subtypes of ALS: Retrotransposon Activation, Oxidative Stress, and Activated Glia
Homo sapiens · GPL16791
An in situ method for identification of transcriptome-wide protein-RNA interactions in cells [in_situ_STAMP]
Mus musculus · GPL24247
An in situ method for identification of transcriptome-wide protein-RNA interactions in cells [eCLIP-seq ]
Mus musculus · GPL21103
An in situ method for identification of transcriptome-wide protein-RNA interactions in cells [isSTAMP]
Mus musculus · GPL30172
Aging-linked deterioration of RNA metabolism destabilizes the stress response of neurons [RNA-seq]
Homo sapiens · GPL24676
Aging-linked deterioration of RNA metabolism destabilizes the stress response of neurons [eCLIP-seq]
Mus musculus · GPL24676
Aging-linked deterioration of RNA metabolism destabilizes the stress response of neurons [RNASeq, RiboSeq]
Homo sapiens · GPL24676
Investigational eIF2B activator DNL343 modulates the Integrated Stress Response in Preclinical Models of TDP-43 Pathology.
Homo sapiens · GPL24676
Distinct and shared molecular targets and functions of ALS-associated TDP-43, FUS, and TAF15 revealed by comprehensive multi-system integrative analyses [CLIP-Seq]
Mus musculus · GPL13112
Distinct and shared functions of ALS-associated TDP-43, FUS, and TAF15 revealed by comprehensive multi-system integrative analyses [RNA-Seq_human]
Homo sapiens · GPL11154
Distinct and shared functions of ALS-associated TDP-43, FUS, and TAF15 revealed by comprehensive multi-system integrative analyses [RNA-Seq_mouse]
Mus musculus · GPL13112
Divergent roles of ALS-linked proteins FUS/TLS and TDP-43 intersect in processing long pre-mRNAs (RNA-Seq)
Mus musculus · GPL9250
Disrupted processing of long pre-mRNAs and widespread RNA missplicing are components of neuronal vulnerability from loss of nuclear TDP-43 (Affymetrix)
Mus musculus · GPL13185
Distinct and shared functions of ALS-associated TDP-43, FUS, and TAF15 revealed by comprehensive multi-system integrative analyses [array]
Mus musculus · GPL13185
Divergent roles of ALS-linked proteins FUS/TLS and TDP-43 intersect in processing long pre-mRNAs (microarray)
Mus musculus · GPL13185
Disrupted processing of long pre-mRNAs and widespread RNA missplicing are components of neuronal vulnerability from loss of nuclear TDP-43 (CLIP)
Mus musculus · GPL9250
Showing first 25 dataset results.
Analyses 23
GSE137810 · 8 steps · GSE · code_examples
Investigational eIF2B activator DNL343 modulates the integrated stress response in preclinical models of TDP-43 pathology and individuals with ALS in … (2025)
GSE281960 · 10 steps · GSE · code_examples
Investigational eIF2B activator DNL343 modulates the integrated stress response in preclinical models of TDP-43 pathology and individuals with ALS in … (2025)
GSE25421 · 1 step · GSE · code_examples
Inhibition of RNA splicing triggers CHMP7 nuclear entry, impacting TDP-43 function and leading to the onset of ALS cellular phenotypes. (2024)
GSE121569 · 12 steps · RNA-Seq · code_examples
Aberrant NOVA1 function disrupts alternative splicing in early stages of amyotrophic lateral sclerosis. (2022)
GSE122069 · 2 steps · RNA-Seq · code_examples
Aberrant NOVA1 function disrupts alternative splicing in early stages of amyotrophic lateral sclerosis. (2022)
GSE56504 · 2 steps · GSE · code_examples
Aberrant NOVA1 function disrupts alternative splicing in early stages of amyotrophic lateral sclerosis. (2022)
GSE65973 · 5 steps · RNA-Seq · code_examples
Aberrant NOVA1 function disrupts alternative splicing in early stages of amyotrophic lateral sclerosis. (2022)
GSE103225 · 32 steps · RIP-Seq · code_examples
Transcriptome-pathology correlation identifies interplay between TDP-43 and the expression of its kinase CK1E in sporadic ALS. (2018)
GSE76220 · 5 steps · RNA-Seq · code_examples
Transcriptome-pathology correlation identifies interplay between TDP-43 and the expression of its kinase CK1E in sporadic ALS. (2018)
GSE77699 · 2 steps · GSE · code_examples
Distinct and shared functions of ALS-associated proteins TDP-43, FUS and TAF15 revealed by multisystem analyses. (2016)
GSE77700 · 3 steps · RIP-Seq · code_examples
Distinct and shared functions of ALS-associated proteins TDP-43, FUS and TAF15 revealed by multisystem analyses. (2016)
GSE77702 · 5 steps · RNA-Seq · code_examples
Distinct and shared functions of ALS-associated proteins TDP-43, FUS and TAF15 revealed by multisystem analyses. (2016)
GSE77703 · 5 steps · RNA-Seq · code_examples
Distinct and shared functions of ALS-associated proteins TDP-43, FUS and TAF15 revealed by multisystem analyses. (2016)
GSE77704 · 5 steps · RNA-Seq · code_examples
Distinct and shared functions of ALS-associated proteins TDP-43, FUS and TAF15 revealed by multisystem analyses. (2016)
GSE77707 · 2 steps · GSE · code_examples
Distinct and shared functions of ALS-associated proteins TDP-43, FUS and TAF15 revealed by multisystem analyses. (2016)
GSE40649 · 2 steps · GSE · code_examples
Divergent roles of ALS-linked proteins FUS/TLS and TDP-43 intersect in processing long pre-mRNAs. (2012)
GSE40651 · 1 step · RNA-Seq · code_examples
Divergent roles of ALS-linked proteins FUS/TLS and TDP-43 intersect in processing long pre-mRNAs. (2012)
GSE40652 · 1 step · RNA-Seq · code_examples
Divergent roles of ALS-linked proteins FUS/TLS and TDP-43 intersect in processing long pre-mRNAs. (2012)
GSE40653 · 2 steps · GSE · code_examples
Divergent roles of ALS-linked proteins FUS/TLS and TDP-43 intersect in processing long pre-mRNAs. (2012)
GSE27201 · 1 step · RNA-Seq · code_examples
Long pre-mRNA depletion and RNA missplicing contribute to neuronal vulnerability from loss of TDP-43. (2011)
GSE27218 · 1 step · RNA-Seq · code_examples
Long pre-mRNA depletion and RNA missplicing contribute to neuronal vulnerability from loss of TDP-43. (2011)
GSE27371 · 2 steps · GSE · code_examples
Long pre-mRNA depletion and RNA missplicing contribute to neuronal vulnerability from loss of TDP-43. (2011)
GSE27394 · 1 step · GSE · code_examples
Long pre-mRNA depletion and RNA missplicing contribute to neuronal vulnerability from loss of TDP-43. (2011)