ReviewFrontiers in molecular biosciences2019
To Be or Not To Be…Toxic-Is RNA Association With TDP-43 Complexes Deleterious or Protective in Neurodegeneration?
Review in Frontiers in molecular biosciences, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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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.
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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
16 citing papers in PubMed, 27 citations in OpenAlex.
- From Evasion to Collapse: The Kinetic Cascade of TDP-43 and the Failure of Proteostasis.International journal of molecular sciences · 2026Review
- Sephin1 reduces TDP-43 cytoplasmic mislocalization and improves motor neuron survival in ALS models.Life science alliance · 2025Article
- Co-Aggregation of TDP-43 with Other Pathogenic Proteins and Their Co-Pathologies in Neurodegenerative Diseases.International journal of molecular sciences · 2024Review
- TDP-43 in nuclear condensates: where, how, and why.Biochemical Society transactions · 2024Review
- Hetero-oligomerization of TDP-43 carboxy-terminal fragments with cellular proteins contributes to proteotoxicity.Communications biology · 2024Article
- Implications of TDP-43 in non-neuronal systems.Cell communication and signaling : CCS · 2023Review
- Limbic-predominant age-related TDP43 encephalopathy (LATE) neuropathological change in neurodegenerative diseases.Nature reviews. Neurology · 2023Review
- Article
- Sequence- and structure-specific RNA oligonucleotide binding attenuates heterogeneous nuclear ribonucleoprotein A1 dysfunction.Frontiers in molecular biosciences · 2023Article
- DDX1 vesicles control calcium-dependent mitochondrial activity in mouse embryos.Nature communications · 2022Article
- New lessons on TDP-43 from old N. furzeri killifish.Aging cell · 2022Article
- Synaptic dysfunction in ALS and FTD: anatomical and molecular changes provide insights into mechanisms of disease.Frontiers in molecular neuroscience · 2022Review
- Prionoids in amyotrophic lateral sclerosis.Brain communications · 2022Review
- BMP/TGF-β signaling as a modulator of neurodegeneration in ALS.Developmental dynamics : an official publication of the American Association of Anatomists · 2022Article
- Mechanisms of TDP-43 Proteinopathy Onset and Propagation.International journal of molecular sciences · 2021Review
- Praja1 RING-finger E3 ubiquitin ligase suppresses neuronal cytoplasmic TDP-43 aggregate formation.Neuropathology : official journal of the Japanese Society of Neuropathology · 2020Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
TAR DNA binding protein (TDP-43) is a nucleic acid binding protein associated with insoluble cytoplasmic aggregates in several neurodegenerative disorders, including 97% of the ALS cases. In healthy individuals, TDP-43 is primarily localized to the nucleus; it can shuttle between the nucleus and the cytoplasm, and is involved in several aspects of RNA processing including transcription, splicing, RNA stability, transport, localization, stress granule (SG) formation, and translation. Upon stress, TDP-43 aggregates in the cytoplasm and associates with several types of RNA and protein assemblies, resulting in nuclear depletion of TDP-43. Under conditions of prolonged stress, cytoplasmic TDP-43 undergoes liquid-liquid phase separation (LLPS) and becomes less mobile. Evidence exists to support a scenario in which insoluble TDP-43 complexes sequester RNA and/or proteins causing disturbances in both ribostasis and proteostasis, which in turn contribute to neurodegeneration. However, the relationship between RNA binding and TDP-43 toxicity remains unclear. Recent studies provide conflicting views on the role of RNA in TDP-43 toxicity, with some finding RNA as a toxic factor whereby RNA binding contributes to TDP-43 toxicity, while others find RNA to be a protective factor that inhibits TDP-43 aggregation. Here we review and discuss these recent reports, which ultimately highlight the importance of understanding the heterogeneity of TDP-43 assemblies and collectively point to solubilizing TDP-43 as a potential therapeutic strategy.
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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.