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激活 Sirt1/NF-κB 通路对神经紊乱的保护作用。

The protective effects of activating Sirt1/NF-κB pathway for neurological disorders.

机构信息

Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang 110004, China.

出版信息

Rev Neurosci. 2021 Nov 8;33(4):427-438. doi: 10.1515/revneuro-2021-0118. Print 2022 Jun 27.

Abstract

Sirt1, a member of the sirtuins family, is a nicotinamide adenosine dinucleotide (NAD)-dependent deacetylase. It can be involved in the regulation of several processes including inflammatory response, apoptosis, oxidative stress, energy metabolism, and autophagy by exerting deacetylation. Nuclear factor-κB (NF-κB), a crucial nuclear transcription factor with specific DNA binding sequences, exists in almost all cells and plays a vital role in several biological processes involving inflammatory response, immune response, and apoptosis. As the hub of multiple intracellular signaling pathways, the activity of NF-κB is regulated by multiple factors. Sirt1 can both directly deacetylate NF-κB and indirectly through other molecules to inhibit its activity. We would like to emphasize that Sirt1/NF-κB is a signaling pathway that is closely related to neuroinflammation. Many recent studies have demonstrated the neuroprotective effects of Sirt1/NF-κB signaling pathway activation applied to the treatment of neurological related diseases. In this review, we focus on new advances in the neuroprotective effects of the Sirt1/NF-κB pathway. First, we briefly review Sirt1 and NF-κB, two key molecules of cellular metabolism. Next, we discuss the connection between NF-κB and neuroinflammation. In addition, we explore how Sirt1 regulates NF-κB in nerve cells and relevant evidence. Finally, we analyze the therapeutic effects of the Sirt1/NF-κB pathway in several common neuroinflammation-related diseases.

摘要

Sirt1 是烟酰胺腺嘌呤二核苷酸(NAD)依赖性去乙酰化酶家族的一员。它可以通过去乙酰化作用参与调节几种过程,包括炎症反应、细胞凋亡、氧化应激、能量代谢和自噬。核因子-κB(NF-κB)是一种具有特定 DNA 结合序列的关键核转录因子,几乎存在于所有细胞中,在涉及炎症反应、免疫反应和细胞凋亡的几个生物学过程中发挥着重要作用。作为多个细胞内信号通路的枢纽,NF-κB 的活性受到多种因素的调节。Sirt1 可以直接对 NF-κB 进行去乙酰化,也可以通过其他分子间接抑制其活性。我们要强调的是,Sirt1/NF-κB 是一个与神经炎症密切相关的信号通路。许多最近的研究表明,激活 Sirt1/NF-κB 信号通路对治疗神经相关疾病具有神经保护作用。在这篇综述中,我们重点介绍了 Sirt1/NF-κB 通路在神经保护方面的新进展。首先,我们简要回顾了细胞代谢的两个关键分子 Sirt1 和 NF-κB。接下来,我们讨论了 NF-κB 与神经炎症之间的联系。此外,我们探讨了 Sirt1 如何在神经细胞中调节 NF-κB 及其相关证据。最后,我们分析了 Sirt1/NF-κB 通路在几种常见的神经炎症相关疾病中的治疗效果。

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