ArticlePloS one2013
Inhibition of TDP-43 aggregation by nucleic acid binding.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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
40 citing papers in PubMed, 76 citations in OpenAlex.
- VAEBAC: a representation-learning framework for proteome-scale prediction of amyloidogenic proteins and functional stratification of nucleic-acid-binding proteins.Bioinformatics (Oxford, England) · 2026Article
- TDP-43 proteinopathy as a biomarker and therapeutic target in amyotrophic lateral sclerosis.Biochemical Society transactions · 2026Review
- AI-discovered protein fragments as generalizable regulators of biomolecular condensates.bioRxiv : the preprint server for biology · 2026Article
- Isoform-specific steric zippers drive aberrant assembly and mislocalization of shortened TDP-43.Science advances · 2026Article
- Molecular Mechanisms of Protein Aggregation in ALS-FTD: Focus on TDP-43 and Cellular Protective Responses.Cells · 2025Review
- Hydrogen-Deuterium Exchange Mass Spectrometry Reveals Mechanistic Insights into RNA Oligonucleotide-Mediated Inhibition of TDP-43 Aggregation.Journal of the American Chemical Society · 2024Article
- RNA binding tunes the conformational plasticity and intradomain stability of TDP-43 tandem RNA recognition motifs.Biophysical journal · 2024Article
- Review
- Structural Insights into Seeding Mechanisms of hIAPP Fibril Formation.Journal of the American Chemical Society · 2024Article
- Recombinant Full-Length TDP-43 Oligomers Retain Their Ability to Bind RNAs, Are Not Toxic, and Do Not Seed TDP-43 Aggregation in Vitro.ACS chemical neuroscience · 2024Article
- Protein aggregation and therapeutic strategies in SOD1- and TDP-43- linked ALS.Frontiers in molecular biosciences · 2024Review
- Altered TDP-43 Structure and Function: Key Insights into Aberrant RNA, Mitochondrial, and Cellular and Systemic Metabolism in Amyotrophic Lateral Sclerosis.Metabolites · 2022Review
- Mechanistic and Therapeutic Insights into Ataxic Disorders with Pentanucleotide Expansions.Cells · 2022Review
- Insights into the aggregation mechanism of RNA recognition motif domains in TDP-43: a theoretical exploration.Royal Society open science · 2021Article
- Mechanisms of TDP-43 Proteinopathy Onset and Propagation.International journal of molecular sciences · 2021Review
- N-terminal Domain of TDP43 Enhances Liquid-Liquid Phase Separation of Globular Proteins.Journal of molecular biology · 2021Article
- Tandem RNA binding sites induce self-association of the stress granule marker protein TIA-1.Nucleic acids research · 2021Article
- The Impact of ALS-Associated GenesCells · 2020Article
- Tau-mediated dysregulation of RNA: Evidence for a common molecular mechanism of toxicity in frontotemporal dementia and other tauopathies.Neurobiology of disease · 2020Review
- Amyotrophic Lateral Sclerosis: Proteins, Proteostasis, Prions, and Promises.Frontiers in cellular neuroscience · 2020Article
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 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The aggregation of TAR DNA-binding protein (TDP-43) has been shown as a hallmark of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) since 2006. While evidence has suggested that mutation or truncation in TDP-43 influences its aggregation process, nevertheless, the correlation between the TDP-43 aggregation propensity and its binding substrates has not been fully established in TDP-43 proteinopathy. To address this question, we have established a platform based on the in vitro protein expression system to evaluate the solubility change of TDP-43 in response to factors such as nucleotide binding and temperature. Our results suggest that the solubility of TDP-43 is largely influenced by its cognate single-strand DNA (ssDNA) or RNA (ssRNA) rather than hnRNP, which is known to associate with TDP-43 C-terminus. The direct interaction between the refolded TDP-43, purified from E.coli, and ssDNA were further characterized by Circular Dichroism (CD) as well as turbidity and filter binding assay. In addition, ssDNA or ssRNA failed to prevent the aggregation of the F147L/F149L double mutant or truncated TDP-43 (TDP208-414). Consistently, these two mutants form aggregates, in contrast with the wild-type TDP-43, when expressed in Neuro2a cells. Our results demonstrate an intimate relationship between the solubility of TDP-43 and its DNA or RNA binding affinity, which may shed light on the role of TDP-43 in ALS and FTLD.
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.