ReviewThe Lancet. Neurology2025
Amyotrophic lateral sclerosis caused by TARDBP mutations: from genetics to TDP-43 proteinopathy.
Review in The Lancet. Neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 2 of them syntheses 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
35 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Non-Invasive Brain Stimulation for Amyotrophic Lateral Sclerosis: Current Evidence and Future Perspectives.Medicina (Kaunas, Lithuania) · 2025Pooled it
- Efficacy and safety of pharmacological and biological therapies for amyotrophic lateral sclerosis: a network meta-analysis.Frontiers in neurologyPooled it
- Review
- The Prospective Regulatory Functions of lncRNAs and Their ceRNA Networks in the Development of Motor Neurons and Associated Diseases.Biomolecules · 2026Review
- Regenerative strategies for ALS: stem cells and extracellular vesicles.Discover nano · 2026Review
- TDP-43 controls RNA structure through high affinity lattice interactions.Nature communications · 2026Article
- A complete genome for the common marmoset.Cell · 2026Article
- Intron retention in health and amyotrophic lateral sclerosis.Brain : a journal of neurology · 2026Review
- Neuroprotective Effects of RNS60 in TDP-43 Pathology-Associated Amyotrophic Lateral Sclerosis.Muscle & nerve · 2026Article
- Review
- Multi-hit genetic lesions and a stress-imprinted immune transcriptome define the inflammatory pathology in ALS patients.Research square · 2026Article
- TDP-43 Aggregation: The Healthy-Toxic Balance of the Prion-Like Domain.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- TDP-43 oxidation and PP1 crosstalk at RNA granule-mitochondria contact sites.Nature communications · 2026Article
- Distinct UNC13A Haplotype Blocks Define Disease Severity and Survival in Chinese Amyotrophic Lateral Sclerosis.European journal of neurology · 2026Article
- Review
- TDP-43: [GU]-ardian of the transcriptome.Molecular neurodegeneration · 2026Review
- FTDP-17T Mutations Promote Formation of Phosphorylated FTDP-17T TAU Oligomers That Cause Degeneration of Dopaminergic and Hippocampal Neurons via Activating ER Stress and Mitochondrial Pro-apoptotic Cascades.Neurochemical research · 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
- Paraspeckle condensation is controlled via TDP-43 polymerization and linked to neuroprotection.Nature cell biology · 2026Article
- A Complete Genome for the Common Marmoset.bioRxiv : the preprint server for biology · 2026Article
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.
Funding
Abstract
Mutations in the TARDBP gene, which encodes the TDP-43 protein, account for only 3-5% of familial cases of amyotrophic lateral sclerosis and less than 1% of cases that are apparently idiopathic. However, the discovery of neuronal inclusions of TDP-43 as the neuropathological hallmark in the majority of cases of amyotrophic lateral sclerosis has transformed our understanding of the pathomechanisms underlying neurodegeneration. An individual TARDBP mutation can cause phenotypic heterogeneity. Most mutations lie within the C-terminus of the TDP-43 protein. In pathological conditions, TDP-43 is mislocalised from the nucleus to the cytoplasm, where it can be phosphorylated, cleaved, and form insoluble aggregates. This mislocalisation leads to dysfunction of downstream pathways of RNA metabolism, proteostasis, mitochondrial function, oxidative stress, axonal transport, and local translation. Biomarkers for TDP-43 dysfunction and targeted therapies are being developed, justifying cautious optimism for personalised medicine approaches that could rescue the downstream effects of TDP-43 pathology.
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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.