ArticleNature neuroscience2019
TDP-43 extracted from frontotemporal lobar degeneration subject brains displays distinct aggregate assemblies and neurotoxic effects reflecting disease progression rates.
Article in Nature neuroscience, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 123 papers.
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Who cites it
123 citing papers in PubMed, 200 citations in OpenAlex.
- Peripheral TDP-43 pathology in amyotrophic lateral sclerosis: toward a systemic proteinopathy.Acta neuropathologica · 2026Review
- Prion-like Protein TDP-43: Mechanisms, Diagnosis, and Therapeutic Prospects.Pathogens (Basel, Switzerland) · 2026Review
- A phosphorylation‑independent monoclonal antibody improves detection of TDP‑43 pathology across frontotemporal lobar degeneration, amyotrophic lateral sclerosis, and limbic predominant age related TDP‑43 encephalopathy neuropathological change.Journal of neuropathology and experimental neurology · 2026Article
- Protein thiol alterations drive pathologic liquid-liquid phase separation in the aging brain.Nature structural & molecular biology · 2026Article
- Concentration-dependent cytoplasmic phase separation of TDP-43 drives aggregation and proteinopathy.The FEBS journal · 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
- Blocking RAN translation without altering repeat RNAs rescuesScience (New York, N.Y.) · 2026Article
- Understanding liquid-liquid phase separation through TDP-43: fundamental principles, subcellular compartmentalisation, and role of solid inclusion formation.Genome biology · 2026Review
- Ubiquitin Proteasome System Components, RAD23A and USP13, Modulate TDP-43 Solubility and Neuronal Toxicity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Pathological TDP-43 filaments accumulate at synapses and cause synaptic dysfunction.bioRxiv : the preprint server for biology · 2026Article
- Reduction of RAD23A extends lifespan and mitigates pathology in a mouse model of TDP-43 proteinopathy.Nature communications · 2026Article
- Aberrant NSUN1 activity connects mLife science alliance · 2026Article
- Transcriptomic and pathological analysis of the hnRNP network reveals glial involvement in frontotemporal lobar degeneration pathological subtypes.Brain communications · 2026Article
- Lysosomal escape and TMEM106B fibrillar core determine TDP-43 seeding outcomes.bioRxiv : the preprint server for biology · 2025Article
- Direct interaction between TDP-43 and Tau promotes their co-condensation, while suppressing Tau fibril formation and seeding.The EMBO journal · 2025Article
- The molecular mechanism of uptake and cell-to-cell transmission of arginine-containing dipeptide repeat proteins.bioRxiv : the preprint server for biology · 2025Article
- Development of [Nature communications · 2025Article
- A single dose of a vectorized mAb targeting TDP-43 potently inhibits the neuropathology in a model of ALS/FTD.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Perspectives in Amyotrophic Lateral Sclerosis: Biomarkers, Omics, and Gene Therapy Informing Disease and Treatment.International journal of molecular sciences · 2025Review
63 more citing papers are in PubMed but not listed here.
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Authors and funding
23 authors at 8 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Accumulation of abnormally phosphorylated TDP-43 (pTDP-43) is the main pathology in affected neurons of people with amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Morphological diversity and neuroanatomical distribution of pTDP-43 accumulations allowed classification of FTLD cases into at least four subtypes, which are correlated with clinical presentations and genetic causes. To understand the molecular basis of this heterogeneity, we developed SarkoSpin, a new method for biochemical isolation of pathological TDP-43. By combining SarkoSpin with mass spectrometry, we revealed proteins beyond TDP-43 that become abnormally insoluble in a disease subtype-specific manner. We show that pTDP-43 extracted from brain forms stable assemblies of distinct densities and morphologies that are associated with disease subtypes. Importantly, biochemically extracted pTDP-43 assemblies showed differential neurotoxicity and seeding that were correlated with disease duration of FTLD subjects. Our data are consistent with the notion that disease heterogeneity could originate from alternate pathological TDP-43 conformations, which are reminiscent of prion strains.
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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.