ChemR23 activation attenuates cognitive impairment in chronic cerebral hypoperfusion by inhibiting NLRP3 inflammasome-induced neuronal pyroptosis.
ChemR23 activation attenuates cognitive impairment in chronic cerebral hypoperfusion by inhibiting NLRP3 inflammasome-induced neuronal pyroptosis.
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ChemR23激活通过抑制NLRP 3炎性小体诱导的神经元焦亡减轻慢性脑灌注不足的认知障碍
DOI：
10.1038/s41419-023-06237-6
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发表时间：
2023-11-06
影响因子：
9
通讯作者：
Fu, Jianliang
中科院分区：
文献类型：
--
作者：
Zhang, Yaxuan;Zhang, Jiawei;Zhao, Yao;Zhang, Yueqi;Liu, Lan;Xu, Xiaofeng;Wang, Xiuzhe;Fu, Jianliang
Neuroinflammation plays critical roles in vascular dementia (VaD), the second leading cause of dementia, which can be induced by chronic cerebral hypoperfusion (CCH). NLRP3 inflammasome-induced pyroptosis, the inflammatory programmed cell death, has been reported to contribute to the development of VaD. ChemR23 is a G protein-coupled receptor that has emerging roles in regulating inflammation. However, the role of ChemR23 signalling in NLRP3 inflammasome-induced pyroptosis in CCH remains elusive. In this study, a CCH rat model was established by permanent bilateral common carotid artery occlusion (BCCAO) surgery. Eight weeks after the surgery, the rats were intraperitoneally injected with the ChemR23 agonist Resolvin E1 (RvE1) or chemerin-9 (C-9). Additionally, primary rat hippocampal neurons and SH-SY5Y cells were adopted to mimic CCH injury in vitro. Our results showed that the levels of ChemR23 expression were decreased from the 8th week after BCCAO, accompanied by significant cognitive impairment. Further analysis revealed that CCH induced neuronal damage, synaptic injury and NLRP3-related pyroptosis activation in hippocampal neurons. However, pharmacologic activation of ChemR23 with RvE1 or C-9 counteracted these changes. In vitro experiments also showed that ChemR23 activation prevented primary neuron pyroptosis induced by chronic hypoxia. In addition, manipulating ChemR23 expression markedly regulated NLRP3 inflammasome-induced neuronal pyroptosis through PI3K/AKT/Nrf2 signalling in SH-SY5Y cells under hypoglycaemic and hypoxic conditions. Collectively, our data demonstrated that ChemR23 activation inhibits NLRP3 inflammasome-induced neuronal pyroptosis and improves cognitive function via the PI3K/AKT/Nrf2 signalling pathway in CCH models. ChemR23 may serve as a potential novel therapeutic target to treat CCH-induced cognitive impairment.
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影响因子：
15.9
作者：
Ji RR;Xu ZZ;Strichartz G;Serhan CN
通讯作者：
Serhan CN
影响因子：
2
作者：
Lei, ZeLin;Lu, YaQin;Yu, Qin
通讯作者：
Yu, Qin
27-羟基胆固醇有助于共培养的 SH-SY5Y 细胞和 C6 细胞中溶酶体膜透化介导的细胞焦亡
影响因子：
4.8
作者：
Chen, Si;Zhou, Cui;Xiao, Rong
通讯作者：
Xiao, Rong
影响因子：
5.9
作者：
Bang, Jihye;Kim, Min-Soo;Jeon, Won Kyung
通讯作者：
Jeon, Won Kyung
影响因子：
21.1
作者：
Kennedy AJ;Davenport AP
通讯作者：
Davenport AP