ReviewBrain research2012
TDP-43 aggregation in neurodegeneration: are stress granules the key?
Review in Brain research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 133 papers.
What it found
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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.
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Who cites it
133 citing papers in PubMed, 205 citations in OpenAlex.
- Biomolecular coacervation-mediated materials: Phase states, phase transitions, and biomedical applications.Bioactive materials · 2027Review
- Concentration-dependent cytoplasmic phase separation of TDP-43 drives aggregation and proteinopathy.The FEBS journal · 2026Article
- Site-Specific Raman Probes Reveal Droplet Aging and Residue-Level Fibril Polymorphism in TDP-43Journal of the American Chemical Society · 2026Article
- Kinetics and Spatial Distribution of β-Sheet Development in TDP-43ACS chemical neuroscience · 2026Article
- TSC2 is a stress granule suppressor.bioRxiv : the preprint server for biology · 2026Article
- TDP-43: [GU]-ardian of the transcriptome.Molecular neurodegeneration · 2026Review
- TDP-43 pathology is linked to motor neuron loss and is independent of stress granulesbioRxiv : the preprint server for biology · 2026Article
- ALS and Huntington Disease: Unraveling the Connections between TDP-43 and Huntingtin.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Review
- Reframing TDP-43 in Alzheimer's disease: From co-pathology to neurovascular culprit.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Emergence of Compact Oligomers inside the Small-World Network of TDP-43 Condensates.The journal of physical chemistry letters · 2025Article
- The rheology and interfacial properties of biomolecular condensates.Biophysical reviews · 2025Review
- Genetic Basis of Motor Neuron Diseases: Insights, Clinical Management, and Future Directions.International journal of molecular sciences · 2025Review
- Decoding TDP-43: the molecular chameleon of neurodegenerative diseases.Acta neuropathologica communications · 2024Review
- Pathogenic TDP-43 accelerates the generation of toxic exon1 HTT in Huntington's disease knock-in mice.Aging cell · 2024Article
- RNA binding tunes the conformational plasticity and intradomain stability of TDP-43 tandem RNA recognition motifs.Biophysical journal · 2024Article
- DNAJA2 and Hero11 mediate similar conformational extension and aggregation suppression of TDP-43.RNA (New York, N.Y.) · 2024Article
- The role of biomolecular condensates in protein aggregation.Nature reviews. Chemistry · 2024Review
- The new missense G376V-TDP-43 variant induces late-onset distal myopathy but not amyotrophic lateral sclerosis.Brain : a journal of neurology · 2024Article
- Regulation of stress granule formation in human oligodendrocytes.Nature communications · 2024Article
- Mitigating a TDP-43 proteinopathy by targeting ataxin-2 using RNA-targeting CRISPR effector proteins.Nature communications · 2023Article
73 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
6 authors at 1 institution in 1 country.
Funding
Abstract
The RNA-binding protein TDP-43 is strongly linked to neurodegeneration. Not only are mutations in the gene encoding TDP-43 associated with ALS and FTLD, but this protein is also a major constituent of pathological intracellular inclusions in these diseases. Recent studies have significantly expanded our understanding of TDP-43 physiology. TDP-43 is now known to play important roles in neuronal RNA metabolism. It binds to and regulates the splicing and stability of numerous RNAs encoding proteins involved in neuronal development, synaptic function and neurodegeneration. Thus, a loss of these essential functions is an attractive hypothesis regarding the role of TDP-43 in neurodegeneration. Moreover, TDP-43 is an aggregation-prone protein and, given the role of toxic protein aggregates in neurodegeneration, a toxic gain-of-function mechanism is another rational hypothesis. Importantly, ALS related mutations modulate the propensity of TDP-43 to aggregate in cell culture. Several recent studies have documented that cytoplasmic TDP-43 aggregates co-localize with stress granule markers. Stress granules are cytoplasmic inclusions that repress translation of a subset of RNAs in times of cellular stress, and several proteins implicated in neurodegeneration (i.e. Ataxin-2 and SMN) interact with stress granules. Thus, understanding the interplay between TDP-43 aggregation, stress granules and the effect of ALS-associated TDP-43 mutations may be the key to understanding the role of TDP-43 in neurodegeneration. We propose two models of TDP-43 aggregate formation. The "independent model" stipulates that TDP-43 aggregation is independent of stress granule formation, in contrast to the "precursor model" which presents the idea that stress granule formation contributes to a TDP-43 aggregate "seed" and that chronic stress leads to concentration-dependent TDP-43 aggregation. This article is part of a Special Issue entitled: RNA-Binding Proteins.
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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.