ArticleThe Journal of experimental medicine2011
Deregulation of TDP-43 in amyotrophic lateral sclerosis triggers nuclear factor κB-mediated pathogenic pathways.
Article in The Journal of experimental medicine, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 210 papers, 4 of them syntheses that pooled it.
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Who cites it
210 citing papers in PubMed, 4 syntheses or guidelines pooled it, 335 citations in OpenAlex.
- Insights from meta-analysis and experimental validation identify exosomal miR-146a-5p as a potential biomarker for sporadic amyotrophic lateral sclerosis.Scientific reports · 2025Pooled it
- The DJ1-Nrf2-STING axis mediates the neuroprotective effects of Withaferin A in Parkinson's disease.Cell death and differentiation · 2021Pooled it
- Antibody-Based Therapeutic Interventions for Amyotrophic Lateral Sclerosis: A Systematic Literature Review.Frontiers in neuroscience · 2021Pooled it
- TDP-43 as a possible biomarker for frontotemporal lobar degeneration: a systematic review of existing antibodies.Acta neuropathologica communications · 2015Pooled it
- Aberrant assembly of RNA recognition motif 1 links to pathogenic conversion of TAR DNA-binding protein of 43 kDa (TDP-43).The Journal of biological chemistry · 2013Trial
- Bridging the gap: neuroinflammation and the dawn of precision medicine in amyotrophic lateral sclerosis.Translational neurodegeneration · 2026Review
- TDP-43-immunity-microbiota axis in amyotrophic lateral sclerosis: A potential pathogenic mechanism.Neural regeneration research · 2026Article
- Dynamic integration of skeletal muscle signals via extracellular vesicles in motor neuron diseases.Acta neuropathologica communications · 2026Review
- Physical activity-associated extracellular vesicles inhibit inflammagen-induced microglial activation.Brain, behavior, & immunity - health · 2026Article
- Predictive Cellular Signatures from Live Human Motor Neurons Distinguish TDP-43 ALS and Enable ALS Subtype Stratification.bioRxiv : the preprint server for biology · 2026Article
- Spatiotemporal Dynamics and Cellular States of Neuroinflammation in Amyotrophic Lateral Sclerosis: Implications for Stage‑Specific Therapeutics.ASN neuro · 2026Review
- Region-specific features of early glial activation and Aquaporin-4 dysregulation in conditional mouse models of TDP-43 proteinopathies.Discovery immunology · 2026Article
- A Missense Mutation in Close Proximity of ALS-linked PFN1 Mutations Causes Only Early-onset Paget Disease of Bone.The Journal of clinical endocrinology and metabolism · 2025Article
- Myeloid Irf5 Deficiency Enhances the Therapeutic Efficacy of IMD-0354 in a TDP-25-Induced Neurodegeneration Model.Molecular neurobiology · 2025Article
- Optineurin Shapes Basal and LPS-Induced Transcriptomes in BV2 Microglia.International journal of molecular sciences · 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
- Hospital-treated infections and the risk and prognosis of amyotrophic lateral sclerosis: A population-based study.Journal of internal medicine · 2025Article
- Dysregulation of SELENOI Is Associated with TDP-43 Neuropathology in Amyotrophic Lateral Sclerosis.Cells · 2025Article
- Crossing Barriers: Advancements in Macromolecular Therapeutics for Neurodegenerative Diseases and Strategies to Overcome the Blood-Brain Barrier.ACS pharmacology & translational science · 2025Review
- A Longitudinal Study of Sex Differences in a TDP-43 Mouse Model Reveals STI1 Regulation of TDP-43 Proteinopathy and Motor Deficits.Journal of neurochemistry · 2025Article
150 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
TDP-43 (TAR DNA-binding protein 43) inclusions are a hallmark of amyotrophic lateral sclerosis (ALS). In this study, we report that TDP-43 and nuclear factor κB (NF-κB) p65 messenger RNA and protein expression is higher in spinal cords in ALS patients than healthy individuals. TDP-43 interacts with and colocalizes with p65 in glial and neuronal cells from ALS patients and mice expressing wild-type and mutant TDP-43 transgenes but not in cells from healthy individuals or nontransgenic mice. TDP-43 acted as a co-activator of p65, and glial cells expressing higher amounts of TDP-43 produced more proinflammatory cytokines and neurotoxic mediators after stimulation with lipopolysaccharide or reactive oxygen species. TDP-43 overexpression in neurons also increased their vulnerability to toxic mediators. Treatment of TDP-43 mice with Withaferin A, an inhibitor of NF-κB activity, reduced denervation in the neuromuscular junction and ALS disease symptoms. We propose that TDP-43 deregulation contributes to ALS pathogenesis in part by enhancing NF-κB activation and that NF-κB may constitute a therapeutic target for the disease.
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Registered trials
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.