ArticleStroke and vascular neurology2026
Reduced endothelial TAK1 impairs vascular integrity in cerebral small vessel disease
Article in Stroke and vascular neurology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 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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Who cites it
2 citing papers in PubMed.
- [Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026Article
- The interplay between neuroinflammation and endothelial dysfunction in cerebral small vessel disease.Frontiers in immunology · 2026Review
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHypertension stands as a major modifiable risk factor for cerebral small vessel disease (CSVD), driving pathological cerebrovascular rarefaction and blood-brain barrier (BBB) compromise through endothelial dysfunction and death. However, the mechanisms regulating cerebral endothelial cell death and endogenous vascular repair pathways remain incompletely characterised. While transforming growth factor-β-activated kinase 1 (TAK1) is recognised as a central regulator of cell survival and homeostasis across multiple tissues, its cerebrovascular-specific functions in hypertension-related CSVD pathogenesis have not been fully delineated.
resultsIn RHRSP, chronic hypertension induces predominant necroptosis over apoptosis in cerebral cortical and hippocampal endothelial cells, accompanied by a marked reduction in TAK1 expression. Using genetic and pharmacological approaches, we found that TAK1 downregulation triggers a cascade of pathological events: endothelial necroptosis, tight junction protein degradation, irreversible microvascular rarefaction, BBB leakage and spatial memory deficits. Mechanistically, this cascade is centrally mediated by TAK1-dependent regulation of the receptor-interacting protein kinase 1 (RIPK1)-mixed lineage kinase domain-like (MLKL) axis.
conclusionsOur results demonstrate that TAK1 downregulation in endothelial cells induces RIPK1-MLKL-mediated necroptosis and downregulation of tight junction protein expression. This coordinated mechanism orchestrates cerebrovascular integrity impairment and subsequent cognitive deterioration. This study positions TAK1 as a promising and potential therapeutic target for the prevention and treatment of hypertension-related CSVD.
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