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鸢尾素通过靶向NLRP3炎性小体减轻神经炎症。

Irisin Attenuates Neuroinflammation Targeting the NLRP3 Inflammasome.

作者信息

Filannino Francesca Martina, Ruggiero Melania, Panaro Maria Antonietta, Lofrumento Dario Domenico, Trotta Teresa, Benameur Tarek, Cianciulli Antonia, Calvello Rosa, Zoila Federico, Porro Chiara

机构信息

Department of Clinical and Experimental Medicine, University of Foggia, I-71100 Foggia, Italy.

Department of Biosciences, Biotechnologies and Environment, University of Bari, I-70125 Bari, Italy.

出版信息

Molecules. 2024 Nov 28;29(23):5623. doi: 10.3390/molecules29235623.

DOI:10.3390/molecules29235623
PMID:39683782
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11643767/
Abstract

Neuroinflammation is defined as an immune response involving various cell types, particularly microglia, which monitor the neuroimmune axis. Microglia activate in two distinct ways: M1, which is pro-inflammatory and capable of inducing phagocytosis and releasing pro-inflammatory factors, and M2, which has anti-inflammatory properties. Inflammasomes are large protein complexes that form in response to internal danger signals, activating caspase-1 and leading to the release of pro-inflammatory cytokines such as interleukin 1β. Irisin, a peptide primarily released by muscles during exercise, was examined for its effects on BV2 microglial cells in vitro. Even at low concentrations, irisin was observed to influence the NLRP3 inflammasome, showing potential as a neuroprotective and anti-inflammatory agent after stimulation with lipopolysaccharides (LPSs). Irisin helped maintain microglia in their typical physiological state and reduced their migratory capacity. Irisin also increased Arg-1 protein expression, a marker of M2 polarization, while downregulating NLRP3, Pycard, caspase-1, IL-1β, and CD14. The results of this study indicate that irisin may serve as a crucial mediator of neuroprotection, thus representing an innovative tool for the prevention of neurodegenerative diseases.

摘要

神经炎症被定义为一种涉及多种细胞类型的免疫反应,尤其是监测神经免疫轴的小胶质细胞。小胶质细胞以两种不同的方式激活:M1型,具有促炎作用,能够诱导吞噬作用并释放促炎因子;M2型,具有抗炎特性。炎性小体是一种大型蛋白质复合物,它会响应内部危险信号而形成,激活半胱天冬酶-1并导致促炎细胞因子如白细胞介素1β的释放。鸢尾素是一种主要在运动过程中由肌肉释放的肽,对其在体外对BV2小胶质细胞的作用进行了研究。即使在低浓度下,也观察到鸢尾素会影响NLRP3炎性小体,在脂多糖(LPS)刺激后显示出作为神经保护和抗炎剂的潜力。鸢尾素有助于使小胶质细胞维持在其典型的生理状态,并降低其迁移能力。鸢尾素还增加了M2极化标志物精氨酸酶-1(Arg-1)的蛋白表达,同时下调了NLRP3、凋亡相关斑点样蛋白(Pycard)、半胱天冬酶-1、白细胞介素-1β和CD14。这项研究的结果表明,鸢尾素可能是神经保护的关键介质,因此是预防神经退行性疾病的一种创新工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8ae/11643767/84b5ed34887b/molecules-29-05623-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8ae/11643767/1c280469a508/molecules-29-05623-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8ae/11643767/aa9d236c2848/molecules-29-05623-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8ae/11643767/c954b260d81f/molecules-29-05623-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8ae/11643767/ae4c26442604/molecules-29-05623-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8ae/11643767/a976f52e810a/molecules-29-05623-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8ae/11643767/84b5ed34887b/molecules-29-05623-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8ae/11643767/1c280469a508/molecules-29-05623-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8ae/11643767/aa9d236c2848/molecules-29-05623-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8ae/11643767/c954b260d81f/molecules-29-05623-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8ae/11643767/ae4c26442604/molecules-29-05623-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8ae/11643767/a976f52e810a/molecules-29-05623-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8ae/11643767/84b5ed34887b/molecules-29-05623-g006.jpg

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在tau蛋白病小鼠模型中,鸢尾素通过转录因子A线粒体转录激活因子(TFAM)介导的线粒体代谢抑制小胶质细胞衰老。
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