ArticleNature neuroscience2023
Seeding the aggregation of TDP-43 requires post-fibrillization proteolytic cleavage.
Article in Nature neuroscience, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed.
- Regulation and function of specialized membrane protrusions in intercellular communication.Nature reviews. Molecular cell biology · 2026Review
- Distinct Transcriptional States of TDP-43 Pathology in an Alzheimer's Disease Mouse Model.Neuroscience bulletin · 2026Article
- 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 Aggregation: The Healthy-Toxic Balance of the Prion-Like Domain.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Kinetics and Spatial Distribution of β-Sheet Development in TDP-43ACS chemical neuroscience · 2026Article
- Phosphorylation Mimicking Mutations Cause TDP-43 to Adopt Different Fibril Conformations.bioRxiv : the preprint server for biology · 2026Article
- TDP-43: [GU]-ardian of the transcriptome.Molecular neurodegeneration · 2026Review
- Somatic mosaicism in ALS and FTD identifies focal mutations associated with widespread degeneration.Nature genetics · 2026Article
- PET imaging of alpha-synuclein: from radiotracer design through in vitro and in vivo translation.European journal of nuclear medicine and molecular imaging · 2026Review
- Small heat shock protein HSPB8 interacts with a pre-fibrillar TDP43 low complexity domain species to delay fibril formation.Biophysical chemistry · 2026Article
- Cracking the code of native amyloid fibrils: advances and next steps to enable pathology-informed therapeutic and diagnostic.Nature structural & molecular biology · 2026Review
- Ubiquitin-specific peptidase-19 links TDP-43 aggregation to ER stress.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Chemical and Molecular Strategies in Restoring Autophagic Flux in TDP-43 Proteinopathy.Molecules (Basel, Switzerland) · 2026Review
- A quantitative cell-based reporter links TDP-43 aggregation and dysfunction to define pathogenic mechanisms.PLoS biology · 2026Article
- PML targets and resolves structured protein inclusions to mitigate neurodegeneration.Nature cell biology · 2026Article
- From biomolecular condensates to functional nanomaterials: LLPS-inspired frameworks for nanoscale hydrogels and adaptive materials.Journal of nanobiotechnology · 2026Review
- Elucidation of Molecular Mechanisms of Lipid-Altered Cytotoxicity of TDP-43 Fibrils.ACS chemical neuroscience · 2026Article
- Stress granules as a central hub linking organelle stress, aging, and neurodegeneration.BMB reports · 2026Review
- Pathological TDP-43 filaments accumulate at synapses and cause synaptic dysfunction.bioRxiv : the preprint server for biology · 2026Article
- From Evasion to Collapse: The Kinetic Cascade of TDP-43 and the Failure of Proteostasis.International journal of molecular sciences · 2026Review
Corrections and comments
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Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite the strong evidence linking the transactive response DNA-binding protein 43 (TDP-43) aggregation to the pathogenesis of frontotemporal lobar degeneration with TDP-43, amyotrophic lateral sclerosis and several neurodegenerative diseases, our knowledge of the sequence and structural determinants of its aggregation and neurotoxicity remains incomplete. Herein, we present a new method for producing recombinant full-length TDP-43 filaments that exhibit sequence and morphological features similar to those of brain-derived TDP-43 filaments. We show that TDP-43 filaments contain a β-sheet-rich helical amyloid core that is fully buried by the flanking structured domains of the protein. We demonstrate that the proteolytic cleavage of TDP-43 filaments and exposure of this amyloid core are necessary for propagating TDP-43 pathology and enhancing the seeding of brain-derived TDP-43 aggregates. Only TDP-43 filaments with exposed amyloid core efficiently seeded the aggregation of endogenous TDP-43 in cells. These findings suggest that inhibiting the enzymes mediating cleavage of TDP-43 aggregates represents a viable disease-modifying strategy to slow the progression of amyotrophic lateral sclerosis and other TDP-43 proteinopathies.
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