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25 results for “amyotrophic lateral sclerosis”

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  1. 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 ↗

  2. KIF5A binds RNA to orchestrate synaptic mRNA localization and stress granules in ALS.

    bioRxiv : the preprint server for biology · 2025

    Neuronal health depends on the precise transport and local translation of mRNAs to maintain synaptic function across highly polarized cellular architecture. While kinesin motor proteins are known to mediate mRNA transport, the specificity and direct involvement of individual kinesins as …

    PMID 41279899 DOI ↗

  3. Localized molecular chaperone synthesis maintains neuronal dendrite proteostasis.

    Nature communications · 2024 · 15(1): 10796

    Proteostasis is maintained through regulated protein synthesis and degradation and chaperone-assisted protein folding. However, this is challenging in neuronal projections because of their polarized morphology and constant synaptic proteome remodeling. Using high-resolution fluorescence microscopy, we discover that hippocampal and spinal …

    PMID 39737952 DOI ↗

  4. 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 ↗

  5. Aging RNA granule dynamics in neurodegeneration.

    Frontiers in molecular biosciences · 2022 · 9: 991641

    Disordered RNA-binding proteins and repetitive RNA sequences are the main genetic causes of several neurodegenerative diseases, including amyotrophic lateral sclerosis and Huntington's disease. Importantly, these components also seed the formation of cytoplasmic liquid-like granules, like stress granules and P bodies. …

    PMID 36188213 DOI ↗

  6. 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 ↗

  7. Gain-of-function cardiomyopathic mutations in RBM20 rewire splicing regulation and re-distribute ribonucleoprotein granules within processing bodies.

    Nature communications · 2021 · 12(1): 6324

    Mutations in the cardiac splicing factor RBM20 lead to malignant dilated cardiomyopathy (DCM). To understand the mechanism of RBM20-associated DCM, we engineered isogenic iPSCs with DCM-associated missense mutations in RBM20 as well as RBM20 knockout (KO) iPSCs. iPSC-derived engineered heart …

    PMID 34732726 DOI ↗

  8. Persistent mRNA localization defects and cell death in ALS neurons caused by transient cellular stress.

    Cell reports · 2021 · 36(10): 109685

    Persistent cytoplasmic aggregates containing RNA binding proteins (RBPs) are central to the pathogenesis of late-onset neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS). These aggregates share components, molecular mechanisms, and cellular protein quality control pathways with stress-induced RNA granules (SGs). …

    PMID 34496257 DOI ↗

  9. 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 ↗

  10. Repeat RNA expansion disorders of the nervous system: post-transcriptional mechanisms and therapeutic strategies.

    Critical reviews in biochemistry and molecular biology · 2021 · 56(1): 31-53

    Dozens of incurable neurological disorders result from expansion of short repeat sequences in both coding and non-coding regions of the transcriptome. Short repeat expansions underlie microsatellite repeat expansion (MRE) disorders including myotonic dystrophy (DM1, CUG<sub>50-3,500</sub> in <i>DMPK</i>; DM2, CCTG<sub>75-11,000</sub> in …

    PMID 33172304 DOI ↗

  11. G<sub>4</sub>C<sub>2</sub> Repeat RNA Initiates a POM121-Mediated Reduction in Specific Nucleoporins in C9orf72 ALS/FTD.

    Neuron · 2020 · 107(6): 1124-1140.e11

    Through mechanisms that remain poorly defined, defects in nucleocytoplasmic transport and accumulations of specific nuclear-pore-complex-associated proteins have been reported in multiple neurodegenerative diseases, including C9orf72 Amyotrophic Lateral Sclerosis and Frontotemporal Dementia (ALS/FTD). Using super-resolution structured illumination microscopy, we have explored …

    PMID 32673563 DOI ↗

  12. 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 ↗

  13. Overriding FUS autoregulation in mice triggers gain-of-toxic dysfunctions in RNA metabolism and autophagy-lysosome axis.

    eLife · 2019 · 8

    Mutations in coding and non-coding regions of FUS cause amyotrophic lateral sclerosis (ALS). The latter mutations may exert toxicity by increasing FUS accumulation. We show here that broad expression within the nervous system of wild-type or either of two ALS-linked …

    PMID 30747709 DOI ↗

  14. 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 ↗

  15. Context-Dependent and Disease-Specific Diversity in Protein Interactions within Stress Granules.

    Cell · 2018 · 172(3): 590-604.e13

    Stress granules (SGs) are transient ribonucleoprotein (RNP) aggregates that form during cellular stress and are increasingly implicated in human neurodegeneration. To study the proteome and compositional diversity of SGs in different cell types and in the context of neurodegeneration-linked mutations, …

    PMID 29373831 DOI ↗

  16. Genetic mutations in RNA-binding proteins and their roles in ALS.

    Human genetics · 2017 · 136(9): 1193-1214

    Mutations in genes that encode RNA-binding proteins (RBPs) have emerged as critical determinants of neurological diseases, especially motor neuron disorders such as amyotrophic lateral sclerosis (ALS). RBPs are involved in all aspects of RNA processing, controlling the life cycle of …

    PMID 28762175 DOI ↗

  17. Elimination of Toxic Microsatellite Repeat Expansion RNA by RNA-Targeting Cas9.

    Cell · 2017 · 170(5): 899-912.e10

    Microsatellite repeat expansions in DNA produce pathogenic RNA species that cause dominantly inherited diseases such as myotonic dystrophy type 1 and 2 (DM1/2), Huntington's disease, and C9orf72-linked amyotrophic lateral sclerosis (C9-ALS). Means to target these repetitive RNAs are required for …

    PMID 28803727 DOI ↗

  18. Protein-RNA Networks Regulated by Normal and ALS-Associated Mutant HNRNPA2B1 in the Nervous System.

    Neuron · 2016 · 92(4): 780-795

    HnRNPA2B1 encodes an RNA binding protein associated with neurodegeneration. However, its function in the nervous system is unclear. Transcriptome-wide crosslinking and immunoprecipitation in mouse spinal cord discover UAGG motifs enriched within ∼2,500 hnRNP A2/B1 binding sites and an unexpected role …

    PMID 27773581 DOI ↗

  19. 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 ↗

  20. ALS-causative mutations in FUS/TLS confer gain and loss of function by altered association with SMN and U1-snRNP.

    Nature communications · 2015 · 6: 6171

    The RNA-binding protein FUS/TLS, mutation in which is causative of the fatal motor neuron disease amyotrophic lateral sclerosis (ALS), is demonstrated to directly bind to the U1-snRNP and SMN complexes. ALS-causative mutations in FUS/TLS are shown to abnormally enhance their …

    PMID 25625564 DOI ↗

  21. A novel splice-site mutation in ALS2 establishes the diagnosis of juvenile amyotrophic lateral sclerosis in a family with early onset anarthria and generalized dystonias.

    PloS one · 2014 · 9(12): e113258

    The diagnosis of childhood neurological disorders remains challenging given the overlapping clinical presentation across subgroups and heterogeneous presentation within subgroups. To determine the underlying genetic cause of a severe neurological disorder in a large consanguineous Pakistani family presenting with severe …

    PMID 25474699 DOI ↗

  22. 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 ↗

  23. 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 ↗

  24. 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 ↗

  25. 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+

GSE254209 GSE · GEO

Inhibition of RNA splicing triggers CHMP7 nuclear entry impacting TDP-43 function and leading to onset of ALS (eCLIP).

Homo sapiens · GPL24676

GSE254208 GSE · GEO

Inhibition of RNA splicing triggers CHMP7 nuclear entry impacting TDP-43 function and leading to onset of ALS (RNA-Seq).

Homo sapiens · Illumina

GSE122069 GSE · GEO

Premature polyadenylation-mediated loss of stathmin-2 is a hallmark of TDP-43-dependent neurodegeneration

Homo sapiens · GPL20301

GSE122649 GSE · GEO

Postmortem Cortex Samples Identify Distinct Molecular Subtypes of ALS: Retrotransposon Activation, Oxidative Stress, and Activated Glia [motor cortex]

Homo sapiens · GPL18573

GSE65973 GSE · GEO

RNA sequencing of mice expressing NLS-hTDP-43

Mus musculus · GPL9250

GSE124439 GSE · GEO

Postmortem Cortex Samples Identify Distinct Molecular Subtypes of ALS: Retrotransposon Activation, Oxidative Stress, and Activated Glia

Homo sapiens · GPL16791

GSE18920 GSE · GEO

Sporadic ALS has compartment-specific aberrant exon splicing and altered cell-matrix adhesion biology

Homo sapiens · GPL5188

GSE118347 GSE · GEO

Mutant FUS and ELAVL4 (HuD) aberrant crosstalk in Amyotrophic Lateral Sclerosis

Homo sapiens · GPL20301

GSE50178 GSE · GEO

Identification of FUS RNA targets in HeLa cells

Homo sapiens · GPL9115

GSE51685 GSE · GEO

Targeted degradation of sense and antisense C9orf72 RNA foci as therapy for amyotrophic lateral sclerosis and frontotemporal dementia (strand specific RNA-seq)

Mus musculus · GPL13112

GSE77700 GSE · GEO

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

GSE51741 GSE · GEO

Targeted degradation of sense and antisense C9orf72 RNA foci as therapy for amyotrophic lateral sclerosis and frontotemporal dementia

Mus musculus · GPL11154

GSE77702 GSE · GEO

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

GSE86227 GSE · GEO

HNRNPA2B1 regulates alternative RNA processing in the nervous system and accumulates in granules in ALS IPSC-derived motor neurons [hnRNPA2B1_small_rnaseq]

Mus musculus · GPL15520

GSE77703 GSE · GEO

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

GSE157467 GSE · GEO

Persistent mRNA localization defects and cell death in ALS neurons caused by transient cellular stress

Homo sapiens · GPL20301

GSE86038 GSE · GEO

HNRNPA2B1 regulates alternative RNA processing in the nervous system and accumulates in granules in ALS IPSC-derived motor neurons [hnRNPA2B1_Arrays_human_Fibs_2]

Homo sapiens · GPL15106

GSE86041 GSE · GEO

HNRNPA2B1 regulates alternative RNA processing in the nervous system and accumulates in granules in ALS IPSC-derived motor neurons [iCLIP-seq]

Mus musculus · GPL13112

GSE40652 GSE · GEO

Divergent roles of ALS-linked proteins FUS/TLS and TDP-43 intersect in processing long pre-mRNAs (RNA-Seq)

Mus musculus · GPL9250

GSE51684 GSE · GEO

Targeted degradation of sense and antisense C9orf72 RNA foci as therapy for amyotrophic lateral sclerosis and frontotemporal dementia (Multiplex Analysis of PolyA-linked Sequences)

Homo sapiens · GPL11154

GSE27371 GSE · GEO

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

GSE86218 GSE · GEO

HNRNPA2B1 regulates alternative RNA processing in the nervous system and accumulates in granules in ALS IPSC-derived motor neurons [hnRNPA2B1_Arrays_human_Fibs_1]

Homo sapiens · GPL15106

GSE77699 GSE · GEO

Distinct and shared functions of ALS-associated TDP-43, FUS, and TAF15 revealed by comprehensive multi-system integrative analyses [array]

Mus musculus · GPL13185

GSE40649 GSE · GEO

Divergent roles of ALS-linked proteins FUS/TLS and TDP-43 intersect in processing long pre-mRNAs (microarray)

Mus musculus · GPL13185

GSE86043 GSE · GEO

HNRNPA2B1 regulates alternative RNA processing in the nervous system and accumulates in granules in ALS IPSC-derived motor neurons [hnRNPA2B1_RNA-seq_mouse_SC]

Mus musculus · GPL13112

Showing first 25 dataset results.

Analyses 12

GSE121569 Processing Pipeline

GSE121569 · 12 steps · RNA-Seq · code_examples

Aberrant NOVA1 function disrupts alternative splicing in early stages of amyotrophic lateral sclerosis. (2022)

GSE122069 Processing Pipeline

GSE122069 · 2 steps · RNA-Seq · code_examples

Aberrant NOVA1 function disrupts alternative splicing in early stages of amyotrophic lateral sclerosis. (2022)

GSE122649 Processing Pipeline

GSE122649 · 3 steps · RNA-Seq · code_examples

Aberrant NOVA1 function disrupts alternative splicing in early stages of amyotrophic lateral sclerosis. (2022)

GSE124439 Processing Pipeline

GSE124439 · 2 steps · RNA-Seq · code_examples

Aberrant NOVA1 function disrupts alternative splicing in early stages of amyotrophic lateral sclerosis. (2022)

GSE18920 Processing Pipeline

GSE18920 · 4 steps · GSE · code_examples

Aberrant NOVA1 function disrupts alternative splicing in early stages of amyotrophic lateral sclerosis. (2022)

GSE56504 Processing Pipeline

GSE56504 · 2 steps · GSE · code_examples

Aberrant NOVA1 function disrupts alternative splicing in early stages of amyotrophic lateral sclerosis. (2022)

GSE65973 Processing Pipeline

GSE65973 · 5 steps · RNA-Seq · code_examples

Aberrant NOVA1 function disrupts alternative splicing in early stages of amyotrophic lateral sclerosis. (2022)

GSE118347 Processing Pipeline

GSE118347 · 10 steps · OTHER · code_examples

Gain-of-function cardiomyopathic mutations in RBM20 rewire splicing regulation and re-distribute ribonucleoprotein granules within processing bodies. (2021)

GSE103225 Processing Pipeline

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)

GSE51684 Processing Pipeline

GSE51684 · 4 steps · RNA-Seq · code_examples

Targeted degradation of sense and antisense C9orf72 RNA foci as therapy for ALS and frontotemporal degeneration. (2013)

GSE51685 Processing Pipeline

GSE51685 · 6 steps · RNA-Seq · code_examples

Targeted degradation of sense and antisense C9orf72 RNA foci as therapy for ALS and frontotemporal degeneration. (2013)

GSE51741 Processing Pipeline

GSE51741 · 4 steps · GSE · code_examples

Targeted degradation of sense and antisense C9orf72 RNA foci as therapy for ALS and frontotemporal degeneration. (2013)