ArticleThe Journal of biological chemistry2009
TDP-43 depletion induces neuronal cell damage through dysregulation of Rho family GTPases.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 99 citations in OpenAlex.
- Distinct single-nucleus RNA-seq changes among non-neuronal cells in ADNC, LATE-NC, and mixed pathologies.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- A human Staufen1 BAC transgenic mouse exhibits abnormal autophagy and neurodegeneration across the central nervous system.Cell death & disease · 2026Article
- Dissecting the RNA-binding capacity of the multi-RRM protein Rrm4 essential for endosomal mRNA transport.Nucleic acids research · 2026Article
- A human Staufen1 BAC transgenic mouse exhibits abnormal autophagy and neurodegeneration across the central nervous system.Research square · 2025Article
- ALS-associated RNA-binding proteins promote UNC13A transcription through REST downregulation.The EMBO journal · 2025Article
- Context-dependent Interactors Regulate TDP-43 Dysfunction in ALS/FTLD.bioRxiv : the preprint server for biology · 2025Article
- Downregulation ofBrain communications · 2025Article
- Sustained therapeutic benefits by transient reduction of TDP-43 using ENA-modified antisense oligonucleotides in ALS/FTD mice.Molecular therapy. Nucleic acids · 2023Article
- Hypoxic Preconditioned Neural Stem Cell-Derived Extracellular Vesicles Contain Distinct Protein Cargo from Their Normal Counterparts.Current issues in molecular biology · 2023Article
- Identification of an immune-related gene prognostic index for predicting prognosis, immunotherapeutic efficacy, and candidate drugs in amyotrophic lateral sclerosis.Frontiers in cellular neuroscience · 2022Article
- TDP-43 prevents endogenous RNAs from triggering a lethal RIG-I-dependent interferon response.Cell reports · 2021Article
- The role of TDP-43 mislocalization in amyotrophic lateral sclerosis.Molecular neurodegeneration · 2020Review
- TDP-43 regulates early-phase insulin secretion via CaV1.2-mediated exocytosis in islets.The Journal of clinical investigation · 2019Article
- Cryo-EM structures of four polymorphic TDP-43 amyloid cores.Nature structural & molecular biology · 2019Article
- Amyotrophic lateral sclerosis mutant TDP-43 may cause synaptic dysfunction through altered dendritic spine function.Disease models & mechanisms · 2019Article
- The N Termini of TAR DNA-Binding Protein 43 (TDP43) C-Terminal Fragments Influence Degradation, Aggregation Propensity, and Morphology.Molecular and cellular biology · 2018Article
- Atomic-level evidence for packing and positional amyloid polymorphism by segment from TDP-43 RRM2.Nature structural & molecular biology · 2018Article
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- Chronic oxidative damage together with genome repair deficiency in the neurons is a double whammy for neurodegeneration: Is damage response signaling a potential therapeutic target?Mechanisms of ageing and development · 2017Review
- Article
1 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The 43-kDa TAR DNA-binding protein (TDP-43) is known to be a major component of the ubiquitinated inclusions characteristic of amyotrophic lateral sclerosis and frontotemporal lobar degeneration with ubiquitin-positive inclusions. Although TDP-43 is a nuclear protein, it disappears from the nucleus of affected neurons and glial cells, implicating TDP-43 loss of function in the pathogenesis of neurodegeneration. Here we show that the knockdown of TDP-43 in differentiated Neuro-2a cells inhibited neurite outgrowth and induced cell death. In knockdown cells, the Rho family members RhoA, Rac1, and Cdc42 GTPases were inactivated, and membrane localization of these molecules was reduced. In addition, TDP-43 depletion significantly suppressed protein geranylgeranylation, a key regulating factor of Rho family activity and intracellular localization. In contrast, overexpression of TDP-43 mitigated the cellular damage caused by pharmacological inhibition of geranylgeranylation. Furthermore administration of geranylgeranyl pyrophosphate partially restored cell viability and neurite outgrowth in TDP-43 knockdown cells. In summary, our data suggest that TDP-43 plays a key role in the maintenance of neuronal cell morphology and survival possibly through protein geranylgeranylation of Rho family GTPases.
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