ArticleMolecular neurodegeneration2024
Elevated nuclear TDP-43 induces constitutive exon skipping.
Article in Molecular neurodegeneration, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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22 citing papers in PubMed.
- Human TDP-43 expression worsens FTD-related phenotypes in progranulin-insufficient mice.Neurobiology of disease · 2026Article
- Isoform-specific steric zippers drive aberrant assembly and mislocalization of shortened TDP-43.Science advances · 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
- 4R-tau isoform induction via TDP-43 in neurons in response to insulin: converging signaling pathways with implications for neurodegenerative disease.Acta neuropathologica communications · 2025Article
- Article
- Ptbp1 is not required for retinal neurogenesis and cell fate specification.bioRxiv : the preprint server for biology · 2025Article
- Symptomatic treatment by a BBB-permeable AAV engineered to restore TDP-43 function slows motor neuron disease and prevents paralysis.bioRxiv : the preprint server for biology · 2025Article
- A Slower-Progressing TDP-43 rNLS8 Mouse Model for ALS: Implications for Preclinical and Mechanistic Studies.Neuromolecular medicine · 2025Article
- Large-scale RNA-Seq mining reveals ciclopirox olamine induces TDP-43 cryptic exons.Nature communications · 2025Article
- Critical impact of lysine 136 in TDP-43 phase separation, compartmentalization, and aggregation in living vertebrates.iScience · 2025Article
- Long-read RNA sequencing unveils a novel cryptic exon in MNAT1 along with its full-length transcript structure in TDP-43 proteinopathy.Communications biology · 2025Article
- Inhibition of nonsense-mediated decay in TDP-43 deficient neurons reveals novel cryptic exons.bioRxiv : the preprint server for biology · 2025Article
- Challenges of modelling TDP-43 pathology in mice.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Review
- TDP-43 overexpression in the hypothalamus drives neuropathology, dysregulates metabolism and impairs behavior in mice.Acta neuropathologica communications · 2025Article
- Viral-mediated knockdown of Atxn2 attenuates TDP-43 pathology and muscle dysfunction in the PFN1Acta neuropathologica communications · 2025Article
- Endogenous TDP-43 mislocalization in a novel knock-in mouse model reveals DNA repair impairment, inflammation, and neuronal senescence.Acta neuropathologica communications · 2025Article
- Alternative 3' UTR polyadenylation is disrupted in the rNLS8 mouse model of ALS/FTLD.Molecular brain · 2025Article
- A robust evaluation of TDP-43, poly GP, cellular pathology and behavior in an AAV-C9ORF72 (GActa neuropathologica communications · 2024Article
- A robust evaluation of TDP-43, poly GP, cellular pathology and behavior in a AAV- C9ORF72 (G 4 C 2) 66 mouse model.Research square · 2024Article
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14 authors.
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Abstract
backgroundCytoplasmic inclusions and loss of nuclear TDP-43 are key pathological features found in several neurodegenerative disorders, suggesting both gain- and loss-of-function mechanisms of disease. To study gain-of-function, TDP-43 overexpression has been used to generate in vitro and in vivo model systems.
methodsWe analyzed RNA-seq datasets from mouse and human neurons overexpressing TDP-43 to explore species specific splicing patterns. We explored the dynamics between TDP-43 levels and exon repression in vitro. Furthermore we analyzed human brain samples and publicly available RNA datasets to explore the relationship between exon repression and disease.
resultsOur study shows that excessive levels of nuclear TDP-43 protein lead to constitutive exon skipping that is largely species-specific. Furthermore, while aberrant exon skipping is detected in some human brains, it is not correlated with disease, unlike the incorporation of cryptic exons that occurs after loss of TDP-43.
conclusionsOur findings emphasize the need for caution in interpreting TDP-43 overexpression data and stress the importance of controlling for exon skipping when generating models of TDP-43 proteinopathy.
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