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21 results for “Motor neuron”
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RNA dysregulation as a determinant of aging and neurodegenerative vulnerability.
Trends in cell biology · 2026
In the nervous system, aging causes deterioration of cellular and molecular processes that are associated with declines in cognition, sensory perception, and motor coordination. Aging is also the strongest risk factor for neurodegenerative disease, yet the mechanisms by which aging …
PMID 42711219 DOI ↗
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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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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 ↗
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A splice-switching antisense oligonucleotide approach for pediatric genetic epilepsies.
bioRxiv : the preprint server for biology · 2025
Variants in ion channel genes are common causes of pediatric epilepsy, often leading to intractable seizures, developmental delay and other comorbidities, which increases risk of death. Pathogenic variants in the <i>SCN8A</i> gene, which encodes a voltage-gated sodium channel critical for …
PMID 41278710 DOI ↗
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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 ↗
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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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Localized synthesis of molecular chaperones sustains neuronal proteostasis.
bioRxiv : the preprint server for biology · 2024
Neurons are challenged to maintain proteostasis in neuronal projections, particularly with the physiological stress at synapses to support intercellular communication underlying important functions such as memory and movement control. Proteostasis is maintained through regulated protein synthesis and degradation and chaperone-assisted …
PMID 37873158 DOI ↗
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An RNA-targeting CRISPR-Cas13d system alleviates disease-related phenotypes in Huntington's disease models.
Nature neuroscience · 2023 · 26(1): 27-38
Huntington's disease (HD) is a fatal, dominantly inherited neurodegenerative disorder caused by CAG trinucleotide expansion in exon 1 of the huntingtin (HTT) gene. Since the reduction of pathogenic mutant HTT messenger RNA is therapeutic, we developed a mutant allele-sensitive CAG<sup>EX</sup> …
PMID 36510111 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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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 ↗
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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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Glial cells maintain synapses by inhibiting an activity-dependent retrograde protease signal.
PLoS genetics · 2019 · 15(3): e1007948
Glial cells regulate multiple aspects of synaptogenesis. In the absence of Schwann cells, a peripheral glial cell, motor neurons initially innervate muscle but then degenerate. Here, using a genetic approach, we show that neural activity-regulated negative factors produced by muscle …
PMID 30870413 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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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 ↗
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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 ↗
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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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PPAR-δ is repressed in Huntington's disease, is required for normal neuronal function and can be targeted therapeutically.
Nature medicine · 2016 · 22(1): 37-45
Huntington's disease (HD) is a progressive neurodegenerative disorder caused by a CAG trinucleotide repeat expansion in the huntingtin (HTT) gene, which encodes a polyglutamine tract in the HTT protein. We found that peroxisome proliferator-activated receptor delta (PPAR-δ) interacts with HTT …
PMID 26642438 DOI ↗
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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 ↗
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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 ↗
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 (RNA-Seq).
Homo sapiens · Illumina
Glial cells maintain synapses by inhibiting an activity-dependent retrograde protease signal
Mus musculus · GPL13112
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
Sporadic ALS has compartment-specific aberrant exon splicing and altered cell-matrix adhesion biology
Homo sapiens · GPL5188
Exonuclease assisted mapping of protein-RNA interactions (ePRINT)
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
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
ALS-causative mutations in FUS/TLS confer gain- and loss-of-function by altered association with SMN and U1-snRNP
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
Persistent mRNA localization defects and cell death in ALS neurons caused by transient cellular stress
Homo sapiens · GPL20301
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
HNRNPA2B1 regulates alternative RNA processing in the nervous system and accumulates in granules in ALS IPSC-derived motor neurons [iCLIP-seq]
Mus musculus · GPL13112
Gene Expression Signatures of Motor Neuron Populations Isolated from Sporadic ALS
Homo sapiens · GPL9115
Divergent roles of ALS-linked proteins FUS/TLS and TDP-43 intersect in processing long pre-mRNAs (RNA-Seq)
Mus musculus · GPL9250
HNRNPA2B1 regulates alternative RNA processing in the nervous system and accumulates in granules in ALS IPSC-derived motor neurons
Mus musculus · GPL13112
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
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
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 13
GSE121569 · 12 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)
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)
GSE86038 · 3 steps · GSE · code_examples
Protein-RNA Networks Regulated by Normal and ALS-Associated Mutant HNRNPA2B1 in the Nervous System. (2016)
GSE86040 · 6 steps · RIP-Seq · code_examples
Protein-RNA Networks Regulated by Normal and ALS-Associated Mutant HNRNPA2B1 in the Nervous System. (2016)
GSE86041 · 7 steps · RIP-Seq · code_examples
Protein-RNA Networks Regulated by Normal and ALS-Associated Mutant HNRNPA2B1 in the Nervous System. (2016)
GSE86043 · 8 steps · RNA-Seq · code_examples
Protein-RNA Networks Regulated by Normal and ALS-Associated Mutant HNRNPA2B1 in the Nervous System. (2016)
GSE86218 · 3 steps · GSE · code_examples
Protein-RNA Networks Regulated by Normal and ALS-Associated Mutant HNRNPA2B1 in the Nervous System. (2016)
GSE86223 · 6 steps · GSE · code_examples
Protein-RNA Networks Regulated by Normal and ALS-Associated Mutant HNRNPA2B1 in the Nervous System. (2016)
GSE86224 · 3 steps · GSE · code_examples
Protein-RNA Networks Regulated by Normal and ALS-Associated Mutant HNRNPA2B1 in the Nervous System. (2016)
GSE86227 · 5 steps · ncRNA-Seq · code_examples
Protein-RNA Networks Regulated by Normal and ALS-Associated Mutant HNRNPA2B1 in the Nervous System. (2016)
GSE86462 · 3 steps · GSE · code_examples
Protein-RNA Networks Regulated by Normal and ALS-Associated Mutant HNRNPA2B1 in the Nervous System. (2016)
GSE86464 · 3 steps · GSE · code_examples
Protein-RNA Networks Regulated by Normal and ALS-Associated Mutant HNRNPA2B1 in the Nervous System. (2016)