ArticleScience advances2023
Monomerization of TDP-43 is a key determinant for inducing TDP-43 pathology in amyotrophic lateral sclerosis.
Article in Science advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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48 citing papers in PubMed, 62 citations in OpenAlex.
- TBK1 eliminates aggregation-prone monomeric TDP-43 through an IFNβ-immunoproteasome pathway in ALS models.EMBO reports · 2026Article
- Phase separation in neurodegenerative disorders: a metabolic perspective on protein aggregation and therapeutic targeting.Translational neurodegeneration · 2026Review
- Therapeutic targeting of the conserved region within the low-complexity domain of TDP-43 is neuroprotective and extends survival in amyotrophic lateral sclerosis mice.Nature aging · 2026Article
- TDP-43 proteinopathy as a biomarker and therapeutic target in amyotrophic lateral sclerosis.Biochemical Society transactions · 2026Review
- TDP-43: [GU]-ardian of the transcriptome.Molecular neurodegeneration · 2026Review
- Maintenance and disruption of the physiological dimer structure of TDP-43 in amyotrophic lateral sclerosis and frontotemporal lobar degeneration.BMC medicine · 2026Review
- TMEM106B C-terminal fragments drive nucleocytoplasmic transport failure and TDP-43 mislocalization in the aging human brain.bioRxiv : the preprint server for biology · 2026Article
- TDP43 and hnRNP K Regulate Alternative Splicing of DNAJC5.Cell biology international · 2026Article
- Paraspeckle condensation is controlled via TDP-43 polymerization and linked to neuroprotection.Nature cell biology · 2026Article
- Chemical and Molecular Strategies in Restoring Autophagic Flux in TDP-43 Proteinopathy.Molecules (Basel, Switzerland) · 2026Review
- Neuronal Calcium Signaling and Cytoskeletal Dynamics in Neurodegeneration.International journal of molecular sciences · 2026Review
- Neuronal TDP-43 regulates myelin formation via neurexin 1 mRNA stabilization.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- TDP-43 in neurodegeneration and cancer: Decoding the mechanism of mRNA localization and translation.Biochemistry and biophysics reports · 2026Review
- From Evasion to Collapse: The Kinetic Cascade of TDP-43 and the Failure of Proteostasis.International journal of molecular sciences · 2026Review
- From TDP-43/RNA complex formation to disease-linked TDP-43 aggregation through a structural and cellular approach.Nature communications · 2026Article
- RBM15 affects mitophagy in intracerebral hemorrhage by promoting E2F1 nuclear translocation via NXF1.Frontiers in immunology · 2026Article
- Lysosomal escape and TMEM106B fibrillar core determine TDP-43 seeding outcomes.bioRxiv : the preprint server for biology · 2025Article
- Neurodegeneration Through the Lens of Bioinformatics Approaches: Computational Mechanisms of Protein Misfolding.International journal of molecular sciences · 2025Review
- Dimer-Specific FokT-seq Reveals DNA-Binding Dimerization and Novel Genomic Targets of TDP-43.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- TDP-43 skein-like inclusions are formed by BAG3- and HSP70-guided co-aggregation with actin-binding proteins.Nature cell biology · 2025Article
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Authors and funding
10 authors at 3 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
The cytoplasmic aggregation of TAR DNA binding protein-43 (TDP-43), also known as TDP-43 pathology, is the pathological hallmark of amyotrophic lateral sclerosis (ALS). However, the mechanism underlying TDP-43 cytoplasmic mislocalization and subsequent aggregation remains unclear. Here, we show that TDP-43 dimerization/multimerization is impaired in the postmortem brains and spinal cords of patients with sporadic ALS and that N-terminal dimerization-deficient TDP-43 consists of pathological inclusion bodies in ALS motor neurons. Expression of N-terminal dimerization-deficient mutant TDP-43 in Neuro2a cells and induced pluripotent stem cell-derived motor neurons recapitulates TDP-43 pathology, such as Nxf1-dependent cytoplasmic mislocalization and aggregate formation, which induces seeding effects. Furthermore, TDP-DiLuc, a bimolecular luminescence complementation reporter assay, could detect decreased N-terminal dimerization of TDP-43 before TDP-43 pathological changes caused by the transcription inhibition linked to aberrant RNA metabolism in ALS. These findings identified TDP-43 monomerization as a critical determinant inducing TDP-43 pathology in ALS.
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