ArticleNature communications2021
Axonal TDP-43 condensates drive neuromuscular junction disruption through inhibition of local synthesis of nuclear encoded mitochondrial proteins.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.
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Who cites it
87 citing papers in PubMed, 135 citations in OpenAlex.
- Lateral sclerosis in amyotrophic lateral sclerosis is an upper motor neuron distal axonopathy ("dying back"): a clinical-neuropathological study.Acta neuropathologica · 2026Article
- Multiple motor proteins regulate TDP-43 anterograde axonal transport.Acta neuropathologica · 2026Article
- Synaptic Proteostasis in Health and Disease.Journal of neurochemistry · 2026Review
- Spatial proteomics identifies FXYD6 as a dual-site protein of neuromuscular junction in the diaphragm.Communications biology · 2026Article
- Quantitative Analysis of Axonal Degeneration and TDP-43 Aggregation in Compartmentalized Human iPSC-Derived Motor Neuron-Myotube Co-cultures.Bio-protocol · 2026Article
- Review
- TDP-43 oxidation and PP1 crosstalk at RNA granule-mitochondria contact sites.Nature communications · 2026Article
- TDP-43: [GU]-ardian of the transcriptome.Molecular neurodegeneration · 2026Review
- RNArchitects: how hnRNPs shape neuronal landscapes.Brain : a journal of neurology · 2026Review
- Systemic delivery of synapsin-promoted caveolin-1 overexpression ameliorates pathological TDP-43-induced cognitive decline and neurodegenerative changes.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Review
- Conserved differential expression of DDX helicase and CPEB genes in skeletal muscles potentially influences neuromuscular junctions during aging: a computational analysis.Biogerontology · 2026Article
- Pharmacological modulation of stress granulesFrontiers in pharmacology · 2026Review
- Dysregulated neuronal mRNA transport and translation in FTD/ALS.NPJ dementia · 2026Review
- Vesicular Rps6 Released by Astrocytes in an Experimental Model of AD Regulates Local Translation and Enhances Synaptic Integrity in Neurones.Journal of extracellular vesicles · 2025Article
- The mechanisms underlying TDP-43-associated neurodegeneration in Alzheimer's disease and related dementias.Molecular psychiatry · 2025Review
- Muscle-derived miR-126 regulates TDP-43 axonal local synthesis and NMJ integrity in ALS models.Nature neuroscience · 2025Article
- Antibody targeting TDP-43 mitigates pathogenic pathways induced by the cerebrospinal fluid of ALS.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Dynamic changes in chromosome and nuclear architecture during maturation of normal and ALS C9orf72 motor neurons.bioRxiv : the preprint server for biology · 2025Article
- Blueprint of Collapse: Precision Biomarkers, Molecular Cascades, and the Engineered Decline of Fast-Progressing ALS.International journal of molecular sciences · 2025Review
27 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 6 institutions in 5 countries.
Funding
Abstract
Mislocalization of the predominantly nuclear RNA/DNA binding protein, TDP-43, occurs in motor neurons of ~95% of amyotrophic lateral sclerosis (ALS) patients, but the contribution of axonal TDP-43 to this neurodegenerative disease is unclear. Here, we show TDP-43 accumulation in intra-muscular nerves from ALS patients and in axons of human iPSC-derived motor neurons of ALS patient, as well as in motor neurons and neuromuscular junctions (NMJs) of a TDP-43 mislocalization mouse model. In axons, TDP-43 is hyper-phosphorylated and promotes G3BP1-positive ribonucleoprotein (RNP) condensate assembly, consequently inhibiting local protein synthesis in distal axons and NMJs. Specifically, the axonal and synaptic levels of nuclear-encoded mitochondrial proteins are reduced. Clearance of axonal TDP-43 or dissociation of G3BP1 condensates restored local translation and resolved TDP-43-derived toxicity in both axons and NMJs. These findings support an axonal gain of function of TDP-43 in ALS, which can be targeted for therapeutic development.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.