| Residential College | true |
| Status | 即將出版Forthcoming |
| Artemisinin protects against neural injury by targeting KEAP1 to inhibit ferroptosis in Alzheimer’s disease models | |
Pengxi DENG; ZHENG WENHUA 
| |
| 2024-06 | |
| Conference Name | The 10th Macau Symposium on Biomedical Science |
| Conference Date | 2024-06-13-15 |
| Conference Place | University of Macau,University Hall |
| Abstract | Ferroptosis, a form of cell death characterized by lipid peroxidation, is involved in neurodegenerative diseases like Alzheimer´s disease (AD). Artemisinin, a first-line antimalarial drug, is neuroprotective, but its effect and underlying mechanisms on ferroptosis are unknown. We hypotheses that Artemisinin promotes resistance to neuronal ferroptosis. To test our hypothesis, we investigated the anti-ferroptosis effects of Artemisinin in in vivo and in vitro models. Artemisinin protected against ferroptosis induced by Erastin, with a similar effect to the ferroptosis inhibitor Ferrostatin-1. Moreover, it stimulated the nuclear translocation of Nrf2 and upregulated SLC7A11 and GPX4. Further analysis confirmed that the pharmacological or genetical inhibition of Nrf2, the knockdown of SLC7A11 or GPX4 prevented Artemisinin action, indicating that its anti-ferroptosis effect is mediated by the Nrf2-SLC7A11-GPX4 pathway. Mechanistically, Artemisinin directly targeted KEAP1, promoting the dissociation of KEAP1-Nrf2 complex and inhibiting the ubiquitination of Nrf2. In vivo, Artemisinin inhibited ferroptosis induced by intrahippocampal injection of imidazole-ketone-Erastin (IKE). Moreover, Artemisinin reversed Aβ1-42-induced ferroptosis, lipid peroxidation and glutathione depletion in HT22 cells, primary hippocampal neurons, and 3×Tg mice via the Nrf2-SLC7A11-GPX4 pathway. Our results demonstrate that Artemisinin is a novel neuronal ferroptosis inhibitor that targets KEAP1 to activate the Nrf2-SLC7A11-GPX4 pathway, providing reliable data on the underlying mechanism of Artemisinin's neuroprotective effect against AD. |
| Keyword | Artemisinin, Ferroptosis, Keap1, Nrf2, Alzheimer's Disease (Ad). |
| Document Type | Conference paper |
| Collection | DEPARTMENT OF PHARMACEUTICAL SCIENCES |
| Corresponding Author | ZHENG WENHUA |
| Recommended Citation GB/T 7714 | Pengxi DENG,ZHENG WENHUA. Artemisinin protects against neural injury by targeting KEAP1 to inhibit ferroptosis in Alzheimer’s disease models[C], 2024. |
| APA | Pengxi DENG., & ZHENG WENHUA (2024). Artemisinin protects against neural injury by targeting KEAP1 to inhibit ferroptosis in Alzheimer’s disease models. . |
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