The SIRT-1/Nrf2/HO-1 axis: Guardians of neuronal health in neurological disorders

IF 2.6 3区 心理学 Q2 BEHAVIORAL SCIENCES
Pranshul Sethi , Sidharth Mehan , Zuber Khan , Pankaj Kumar Maurya , Nitish Kumar , Aakash Kumar , Aarti Tiwari , Tarun Sharma , Ghanshyam Das Gupta , Acharan S. Narula , Reni Kalfin
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引用次数: 0

Abstract

SIRT1 (Sirtuin 1) is a NAD+-dependent deacetylase that functions through nucleoplasmic transfer and is present in nearly all mammalian tissues. SIRT1 is believed to deacetylate its protein substrates, resulting in neuroprotective actions, including reduced oxidative stress and inflammation, increased autophagy, increased nerve growth factors, and preserved neuronal integrity in aging or neurological disease. Nrf2 is a transcription factor that regulates the genes responsible for oxidative stress response and substance detoxification. The activation of Nrf2 guards cells against oxidative damage, inflammation, and carcinogenic stimuli. Several neurological abnormalities and inflammatory disorders have been associated with variations in Nrf2 activation caused by either pharmacological or genetic factors. Recent evidence indicates that Nrf2 is at the center of a complex cellular regulatory network, establishing it as a transcription factor with genuine pleiotropy. HO-1 is most likely a component of a defense mechanism in cells under stress, as it provides negative feedback for cell activation and mediator synthesis. This mediator is upregulated by Nrf2, nitric oxide (NO), and other factors in various inflammatory states. HO-1 or its metabolites, such as CO, may mitigate inflammation by modulating signal transduction pathways. Neurological diseases may be effectively treated by modulating the activity of HO-1. Multiple studies have demonstrated that SIRT1 and Nrf2 share an important connection. SIRT1 enhances Nrf2, activates HO-1, protects against oxidative injury, and decreases neuronal death. This has been associated with numerous neurodegenerative and neuropsychiatric disorders. Therefore, activating the SIRT1/Nrf2/HO-1 pathway may help treat various neurological disorders. This review focuses on the current understanding of the SIRT1 and Nrf2/HO-1 neuroprotective processes and the potential therapeutic applications of their target activators in neurodegenerative and neuropsychiatric disorders.
SIRT-1/Nrf2/HO-1轴:神经系统疾病中神经元健康的守护者。
SIRT1(Sirtuin 1)是一种依赖于 NAD+ 的去乙酰化酶,通过核质转移发挥作用,几乎存在于所有哺乳动物组织中。据信,SIRT1 可使其蛋白质底物去乙酰化,从而起到保护神经的作用,包括减少氧化应激和炎症、增加自噬、增加神经生长因子,以及在衰老或神经疾病中保护神经元的完整性。Nrf2 是一种转录因子,可调节负责氧化应激反应和物质解毒的基因。激活 Nrf2 可保护细胞免受氧化损伤、炎症和致癌刺激。一些神经系统异常和炎症性疾病与药物或遗传因素导致的 Nrf2 激活变化有关。最近的证据表明,Nrf2 处于一个复杂的细胞调控网络的中心,使其成为一个具有真正多义性的转录因子。HO-1 很可能是压力下细胞防御机制的一个组成部分,因为它为细胞活化和介质合成提供负反馈。在各种炎症状态下,Nrf2、一氧化氮(NO)和其他因素会上调这种介质。HO-1 或其代谢物(如 CO)可通过调节信号转导途径来缓解炎症。通过调节 HO-1 的活性可以有效治疗神经系统疾病。多项研究表明,SIRT1 和 Nrf2 有着重要的联系。SIRT1 可增强 Nrf2,激活 HO-1,防止氧化损伤,减少神经元死亡。这与许多神经退行性疾病和神经精神疾病有关。因此,激活 SIRT1/Nrf2/HO-1 通路可能有助于治疗各种神经系统疾病。本综述将重点介绍目前对 SIRT1 和 Nrf2/HO-1 神经保护过程的理解,以及其靶向激活剂在神经退行性疾病和神经精神疾病中的潜在治疗应用。
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来源期刊
Behavioural Brain Research
Behavioural Brain Research 医学-行为科学
CiteScore
5.60
自引率
0.00%
发文量
383
审稿时长
61 days
期刊介绍: Behavioural Brain Research is an international, interdisciplinary journal dedicated to the publication of articles in the field of behavioural neuroscience, broadly defined. Contributions from the entire range of disciplines that comprise the neurosciences, behavioural sciences or cognitive sciences are appropriate, as long as the goal is to delineate the neural mechanisms underlying behaviour. Thus, studies may range from neurophysiological, neuroanatomical, neurochemical or neuropharmacological analysis of brain-behaviour relations, including the use of molecular genetic or behavioural genetic approaches, to studies that involve the use of brain imaging techniques, to neuroethological studies. Reports of original research, of major methodological advances, or of novel conceptual approaches are all encouraged. The journal will also consider critical reviews on selected topics.
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