ArticleJCI insight2024
Endothelial TDP-43 controls sprouting angiogenesis and vascular barrier integrity, and its deletion triggers neuroinflammation.
Article in JCI insight, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 19 citations in OpenAlex.
- Retinal Thickness and Vascular Density Changes in Amyotrophic Lateral Sclerosis Assessed by Optical Coherence Tomography Angiography.Biomedicines · 2026Article
- TGF-β signaling promotes astroglial activation and TDP-43 proteinopathy in organoid models of frontotemporal lobar degeneration.The Journal of clinical investigation · 2026Article
- TDP-43: [GU]-ardian of the transcriptome.Molecular neurodegeneration · 2026Review
- VE-cadherin interaction proteomics identifies ARVCF as stabilizer of endothelial adherens junctions.iScience · 2026Article
- Reframing TDP-43 in Alzheimer's disease: From co-pathology to neurovascular culprit.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Skin TDP-43 pathology as a candidate biomarker for predicting amyotrophic lateral sclerosis decades prior to motor symptom onset.bioRxiv : the preprint server for biology · 2025Article
- Pulmonary Hypertension Promotes Neuroinflammation and Neurodegeneration.bioRxiv : the preprint server for biology · 2025Article
- Article
- Challenges of modelling TDP-43 pathology in mice.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Review
- Endothelial TDP-43 depletion disrupts core blood-brain barrier pathways in neurodegeneration.Nature neuroscience · 2025Article
- Amyotrophic lateral sclerosis and frontotemporal dementia mutation reduces endothelial TDP-43 and causes blood-brain barrier defects.Science advances · 2025Article
- Endothelial Dysfunction in Huntington's Disease: Pathophysiology and Therapeutic Implications.International journal of molecular sciences · 2025Review
- Molecular and cellular characteristics of cerebrovascular cell types and their contribution to neurodegenerative diseases.Molecular neurodegeneration · 2025Review
- TDP-43-proteinopathy at the crossroads of tauopathy: on copathology and current and prospective biomarkers.Frontiers in cellular neuroscience · 2025Review
- EndothelialFrontiers in cell and developmental biology · 2025Article
- Increased frontocortical microvascular raspberry density in frontotemporal lobar degeneration compared to Lewy body disease and control cases: a neuropathological study.Free neuropathology · 2025Article
- Endothelial Zmiz1 modulates physiological and pathophysiological angiogenesis during retinal development.bioRxiv : the preprint server for biology · 2024Article
- Limbic-predominant age-related TDP-43 encephalopathy (LATE-NC): Co-pathologies and genetic risk factors provide clues about pathogenesis.Journal of neuropathology and experimental neurology · 2024Review
- Establishment of a novel amyotrophic lateral sclerosis patient (Frontiers in cell and developmental biology · 2024Article
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
TAR DNA-binding protein 43 (TDP-43) is a DNA/RNA-binding protein that regulates gene expression, and its malfunction in neurons has been causally associated with multiple neurodegenerative disorders. Although progress has been made in understanding the functions of TDP-43 in neurons, little is known about its roles in endothelial cells (ECs), angiogenesis, and vascular function. Using inducible EC-specific TDP-43-KO mice, we showed that TDP-43 is required for sprouting angiogenesis, vascular barrier integrity, and blood vessel stability. Postnatal EC-specific deletion of TDP-43 led to retinal hypovascularization due to defects in vessel sprouting associated with reduced EC proliferation and migration. In mature blood vessels, loss of TDP-43 disrupted the blood-brain barrier and triggered vascular degeneration. These vascular defects were associated with an inflammatory response in the CNS with activation of microglia and astrocytes. Mechanistically, deletion of TDP-43 disrupted the fibronectin matrix around sprouting vessels and reduced β-catenin signaling in ECs. Together, our results indicate that TDP-43 is essential for the formation of a stable and mature vasculature.
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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.