ArticleFrontiers in pharmacology2022
DAPT Attenuates Cadmium-Induced Toxicity in Mice by Inhibiting Inflammation and the Notch/HES-1 Signaling Axis.
Article in Frontiers in pharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
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Who cites it
6 citing papers in PubMed, 12 citations in OpenAlex.
- ETS1-EGR2 facilitates renal cell carcinoma progression by activating NOTCH signalling.Clinical and translational medicine · 2026Article
- Notch Signaling Exacerbates Pulmonary Fibrosis by Regulating the Differentiation of CD4Biomolecules · 2026Article
- Norrin in cancer: from a promising prognostic biomarker to a novel therapeutic target.Frontiers in oncology · 2025Review
- Targeting limbal epithelial stem cells: master conductors of corneal epithelial regeneration from the bench to multilevel theranostics.Journal of translational medicine · 2024Review
- Liver organoid culture methods.Cell & bioscience · 2023Review
- Notch Signaling in Acute Inflammation and Sepsis.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The small molecule DAPT inhibits the Notch signaling pathway by blocking γ-secretase mediated Notch cleavage. Given the critical role of the Notch signaling axis in inflammation, we asked whether DAPT could block Notch-mediated inflammation and thus exert neuronal protection. We established a mouse model of chronic exposure to cadmium (Cd)-induced toxicity and treated it with DAPT. DAPT was effective in ameliorating Cd-induced multi-organ damage and cognitive impairment in mice, as DAPT restored abnormal performance in the Y-maze, forced swimming and Morris water maze (MWM) tests. DAPT also reversed Cd-induced neuronal loss and glial cell activation to normal as observed by immunofluorescence and immunohistochemistry of brain tissue sections. In addition, Cd-intoxicated mice showed significantly increased levels of the Notch/HES-1 signaling axis and NF-κB, as well as decreased levels of the inflammatory inhibitors C/EBPβ and COP1. However, DAPT down regulated the elevated Notch/HES-1 signaling axis to normal, eliminating inflammation and thus protecting the nervous system. Thus, DAPT effectively eliminated the neurotoxicity of Cd, and blocking γ-secretase as well as Notch signaling axis may be a potential target for the development of neuronal protective drugs.
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Registered trials
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