| Residential College | true |
| Status | 即將出版Forthcoming |
| Artemisinin Alleviates Astrocyte Over-Activation and Neuroinflammation by modulating the IRE1/NF-κB Signaling Pathway in in vitro and in vivo Alzheimer's Disease Models | |
Lei Chen; 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 | Background: Recent studies have shown that neuroinflammation and heightened glial activity, particularly astrocyte over-activation, are associated with Alzheimer's disease (AD). Abnormal accumulation of Aβ induces endoplasmic reticulum (ER) stress, which activates astrocytes by various signaling pathways, leading to neuroinflammation and neuronal damage. Artemisinin (ART), a frontline anti-malarial drug known for its excellent safety profile and blood-brain barrier permeability, exhibits neuroprotective properties. However, its impact and the underlying mechanisms concerning astrocyte over-activation remain unexplored. Methods: A172 cells, an astrocyte cell line, and primary astrocyte cell cultures treated with Aβ1-42 were used as an in vitro cellular model. 3×Tg-AD mice served as an in vivo animal model to investigate the effects of artemisinin on AD astrocyte over-activation and its intrinsic mechanisms. RT-qPCR, Western blotting, and immunofluorescence were used to measure the mRNA and protein levels. Manipulation of IRE1 expression was achieved through plasmids in vitro and adeno-associated viruses (AAV) in vivo. Results: Aβ1-42 treatment induced astrocyte activation, ER stress, and inflammatory responses in both A172 cells and primary astrocytes. Conversely, artemisinin attenuated the impact of Aβ1-42 by inhibiting IRE1 phosphorylation and the NF-κB pathway, as demonstrated by the overexpression of IRE1 WT and IRE1-K599A (kinase activity invalidated), and application of activators and inhibitors related to ER stress. Furthermore, artemisinin alleviated the detrimental effects of astrocytes on co-cultured neurons, preventing apoptosis during Aβ1-42 treatment. In 3×Tg-AD mice, artemisinin treatment improved cognitive function and reduced astrocyte over-activation, neuroinflammation, ER stress, and neuronal apoptosis. Moreover, artemisinin attenuated the upregulation of IRE1/NF-κB pathway activity in AD mice. This was also demonstrated by the application of drugs to modulate the IRE1/ER stress-related pathway. Furthermore, viruses specifically overexpressing IRE1 in AD mouse astrocytes reversed artemisinin-induced amelioration. Conclusions: Our findings suggest that artemisinin inhibited astrocyte over-activation and neuroinflammation in both in vitro and in vivo AD models by modulating the IRE1/NF-κB signaling pathway, thereby enhancing neuronal functions. This study underscores the therapeutic potential of artemisinin in AD and highlights a promising strategy for targeting the modulation of the ER stress-inflammatory cycle and normalizing astrocyte-neuron communication. |
| Keyword | Alzheimer’s Disease Endoplasmic Reticulum Stress Artemisinin Astrocyte 3xtg Ad Mice Neuroinflammation Ire1 Nf-κb. |
| Document Type | Conference paper |
| Collection | DEPARTMENT OF PHARMACEUTICAL SCIENCES |
| Corresponding Author | ZHENG WENHUA |
| Recommended Citation GB/T 7714 | Lei Chen,ZHENG WENHUA. Artemisinin Alleviates Astrocyte Over-Activation and Neuroinflammation by modulating the IRE1/NF-κB Signaling Pathway in in vitro and in vivo Alzheimer's Disease Models[C], 2024. |
| APA | Lei Chen., & ZHENG WENHUA (2024). Artemisinin Alleviates Astrocyte Over-Activation and Neuroinflammation by modulating the IRE1/NF-κB Signaling Pathway in in vitro and in vivo Alzheimer's Disease Models. . |
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