Notch1

[Petr75]

2018 Nov
The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China
Effect of Notch1 gene on remyelination in multiple sclerosis in mouse models of acute demyelination
https://pubmed.ncbi.nlm.nih.gov/30010211/

.. Our study provided evidence that the inhibition of Notch1 gene could accelerate remyelination in MS.

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2020 Nov 7
Division of Brain Disease Research, Department of Chronic Disease Convergence Research, Korea National Institute of Health,
Osongsaengmyeong, Republic of Korea
Notch1-mediated inflammation is associated with endothelial dysfunction in human brain microvascular endothelial cells upon particulate matter exposure
https://pubmed.ncbi.nlm.nih.gov/33159583/

Abstract

Exposure to atmospheric particulate matter (PM) is an emerging risk factor for the pathogenesis of several diseases in humans, including cerebrovascular diseases. However, the mechanisms underlying PM-induced endothelial dysfunction are currently unclear. In this study, we examined how PM leads to endothelial dysfunction in human brain microvascular endothelial cells (HBMECs). We demonstrated that PM10 exposure (up to 25 μg/mL) increase Notch1 cleavage, and it regulates endothelial dysfunction through NICD-mediated inflammation and senescence. PM10-induced NICD signaling causes increased expression of interleukin-1 beta (IL-1β) and enhances characteristics of cellular senescence, which leads to increased endothelial permeability in HBMECs. Knockdown of Notch1 by siRNA blocks PM10-induced endothelial dysfunction via the suppression of inflammation and senescence. Furthermore, we found that Notch1-mediated inflammation accelerates endothelial senescence, which eventually leads to endothelial dysfunction. Altogether, our data suggest that Notch1 and NICD are potential target regulators for the prevention of cerebrovascular endothelial dysfunction induced by ambient air pollutants such as PM.