ArticleNeurobiology of disease2016
In vitro prion-like behaviour of TDP-43 in ALS.
Article in Neurobiology of disease, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
93 citing papers in PubMed, 1 synthesis or guideline pooled it, 139 citations in OpenAlex.
- A Systematic and Comprehensive Review on Disease-Causing Genes in Amyotrophic Lateral Sclerosis.Journal of molecular neuroscience : MN · 2020Pooled it
- Prion-like Protein TDP-43: Mechanisms, Diagnosis, and Therapeutic Prospects.Pathogens (Basel, Switzerland) · 2026Review
- Pathological TDP-43 filaments accumulate at synapses and cause synaptic dysfunction.bioRxiv : the preprint server for biology · 2026Article
- Beyond motor neurons: peripheral TDP-43 pathology in skeletal muscle and intramuscular nerves in amyotrophic lateral sclerosis.Brain communications · 2026Review
- Lysosomal escape and TMEM106B fibrillar core determine TDP-43 seeding outcomes.bioRxiv : the preprint server for biology · 2025Article
- Putative mitochondrial components of frontotemporal lobar degeneration: topological correlations between mitochondrial density and atrophy in FTLD/FTD phenotypes.Journal of neurology · 2025Article
- The molecular mechanism of uptake and cell-to-cell transmission of arginine-containing dipeptide repeat proteins.bioRxiv : the preprint server for biology · 2025Article
- SOD1, A Crucial Protein for Neural Biochemistry: Dysfunction and Risk of Amyotrophic Lateral Sclerosis.Molecular neurobiology · 2025Review
- Repulsive vs Attractive Crowding Distinctly Regulate TDP-43 Condensates through Region-specific Structural Dynamics.JACS Au · 2025Article
- RNA-binding proteins in ALS and FTD: from pathogenic mechanisms to therapeutic insights.Molecular neurodegeneration · 2025Review
- Exploring Protein Misfolding in Amyotrophic Lateral Sclerosis: Structural and Functional Insights.Biomedicines · 2025Review
- Mild cognitive impairment in amyotrophic lateral sclerosis: current view.Journal of neural transmission (Vienna, Austria : 1996) · 2025Review
- Enhanced secretion of the amyotrophic lateral sclerosis ALS-associated misfolded TDP-43 mediated by the ER-ubiquitin specific peptidase USP19.Cellular and molecular life sciences : CMLS · 2025Article
- TDP-43 as a potential retinal biomarker for neurodegenerative diseases.Frontiers in neuroscience · 2025Review
- The role of microglia in the prion-like transmission of protein aggregates in neurodegeneration.Brain communications · 2025Review
- Co-Aggregation of TDP-43 with Other Pathogenic Proteins and Their Co-Pathologies in Neurodegenerative Diseases.International journal of molecular sciences · 2024Review
- Prion-like Spreading of Disease in TDP-43 Proteinopathies.Brain sciences · 2024Review
- Alzheimer's Disease: Exploring the Landscape of Cognitive Decline.ACS chemical neuroscience · 2024Review
- A Review of Biomarkers of Amyotrophic Lateral Sclerosis: A Pathophysiologic Approach.International journal of molecular sciences · 2024Review
- TDP-43 dysfunction leads to bioenergetic failure and lipid metabolic rewiring in human cells.Redox biology · 2024Article
33 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
Amyotrophic lateral sclerosis (ALS) is the most common form of motor neuron disease (MND), and >95% of familial and sporadic cases involve the deposition of insoluble aggregated, phosphorylated and cleaved TDP-43 protein. Accumulating clinical and biological evidence now indicates that ALS bears a number of similarities to the prion diseases, with TDP-43 acting as a misfolded 'prion-like' protein demonstrating similar underlying pathobiology. Here we systematically address the hypothesis that ALS is a prion-like disorder. First we demonstrate that TDP-43 demonstrates seeded polymerisation in vitro directly from both ALS brain and spinal cord. We next show that the seeding of TDP-43 results in the formation of characteristic insoluble, aggregated, and phosphorylated TDP-43 pathology that directly recapitulates the morphological diversity of TDP-43 inclusions detected in ALS patient CNS tissue. We next demonstrate that this reaction can be serially propagated to produce increasing amounts of phosphorylated TDP-43 pathology, and that aggregates can spread from cell to cell in an analogous fashion to that seen in the prion diseases. Finally, we reproduced our findings in a murine motor neuron-like cell line (NSC-34), where the seeding of TDP-43 induces the formation of TDP-43 oligomers and reduced cell viability. These findings may guide therapeutic strategies in this rapidly progressive and invariably fatal disease.
Indexed as
Identifiers
What OpenQuestion holds
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.