Fan Zhang, Bin Li
Beijing Key Laboratory of Basic Research With Traditional Chinese Medicine (TCM) on Infectious Diseases, Beijing Institute of Chinese Medicine, Beijing Hospital of TCM, Capital Medical University, Beijing, China.
Beijing Key Laboratory of Acupuncture Neuromodulation, Acupuncture and Moxibustion Department, Beijing Hospital of TCM, Capital Medical University, Beijing, China.
Front Cell Neurosci. 2022 Jun 22;16:915587. doi: 10.3389/fncel.2022.915587. eCollection 2022.
Neuroinflammatory disorder is a general term that is associated with the progressive loss of neuronal structure or function. At present, the widely studied diseases with neuroinflammatory components are mainly divided into neurodegenerative and neuropsychiatric diseases, namely, Alzheimer's disease, Parkinson's disease, depression, stroke, and so on. An appropriate neuroinflammatory response can promote brain homeostasis, while excessive neuroinflammation can inhibit neuronal regeneration and damage the central nervous system. Apart from the symptomatic treatment with cholinesterase inhibitors, antidepressants/anxiolytics, and neuroprotective drugs, the treatment of neuroinflammation is a promising therapeutic method. Sirtuins are a host of class III histone deacetylases, that require nicotinamide adenine dinucleotide for their lysine residue deacetylase activity. The role of sirtuin 2 (SIRT2), one of the sirtuins, in modulating senescence, myelin formation, autophagy, and inflammation has been widely studied. SIRT2 is associated with many neuroinflammatory disorders considering it has deacetylation properties, that regulate the entire immune homeostasis. The aim of this review was to summarize the latest progress in regulating the effects of SIRT2 on immune homeostasis in neuroinflammatory disorders. The overall structure and catalytic properties of SIRT2, the selective inhibitors of SIRT2, the relationship between immune homeostasis and SIRT2, and the multitasking role of SIRT2 in several diseases with neuroinflammatory components were discussed.
神经炎症性疾病是一个与神经元结构或功能逐渐丧失相关的通用术语。目前，广泛研究的具有神经炎症成分的疾病主要分为神经退行性疾病和神经精神疾病，即阿尔茨海默病、帕金森病、抑郁症、中风等。适当的神经炎症反应可促进脑内稳态，而过度的神经炎症会抑制神经元再生并损害中枢神经系统。除了使用胆碱酯酶抑制剂、抗抑郁药/抗焦虑药和神经保护药物进行对症治疗外，神经炎症的治疗是一种有前景的治疗方法。沉默调节蛋白是一类III型组蛋白脱乙酰酶，其赖氨酸残基脱乙酰酶活性需要烟酰胺腺嘌呤二核苷酸。沉默调节蛋白2（SIRT2）作为沉默调节蛋白之一，在调节衰老、髓鞘形成、自噬和炎症方面的作用已得到广泛研究。鉴于SIRT2具有调节整个免疫稳态的去乙酰化特性，它与许多神经炎症性疾病相关。这篇综述的目的是总结调节SIRT2对神经炎症性疾病中免疫稳态影响的最新进展。讨论了SIRT2的整体结构和催化特性、SIRT2的选择性抑制剂、免疫稳态与SIRT2的关系以及SIRT2在几种具有神经炎症成分疾病中的多重作用。
