SIRT7 inhibits cerebral ischemic injury by inhibiting microglia M1 polarization via desuccinylation of NAMPT

IF 3.7 3区医学 Q2 NEUROSCIENCES

Brain Research Bulletin Pub Date : 2025-09-16 DOI:10.1016/j.brainresbull.2025.111551

Ying Cheng , Kai Zhao , Jian Li , Qian Lei , Gang Zhang , Xiaoping Gao

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引用次数: 0

Abstract

Cerebral ischemic injury continues to be a leading cause of mortality and disability worldwide. Although Sirtuin 7 (SIRT7), a desuccinylase, is known to regulate protein expression, its role in cerebral ischemia remains unclear. This study utilized a middle cerebral artery occlusion (MCAO) mouse model and an oxygen-glucose deprivation (OGD)-induced microglial model to elucidate the mechanisms of SIRT7. Microglial M1/M2 polarization was assessed via qPCR and immunofluorescence, while underlying mechanisms were analyzed using western blot and co-immunoprecipitation. Our results demonstrated that SIRT7 was significantly downregulated following cerebral ischemic injury. SIRT7 overexpression inhibited OGD-induced M1 polarization, whereas promoting M2 polarization. Mechanistically, SIRT7 mediated nicotinamide phosphoribosyltransferase (NAMPT) desuccinylation and subsequent proteasomal degradation, thereby suppressing M1 polarization and ultimately attenuating brain injury progression. These findings offer novel insights into the regulatory role of SIRT7 in inflammatory responses and suggest that targeting the SIRT7-NAMPT axis could serve as a promising therapeutic strategy for cerebral ischemia-related disorders.

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SIRT7通过NAMPT去琥珀酰化抑制小胶质细胞M1极化，从而抑制脑缺血损伤。

脑缺血损伤仍然是世界范围内死亡和残疾的主要原因。虽然Sirtuin 7 （SIRT7）是一种去琥珀酰化酶，已知可调节蛋白表达，但其在脑缺血中的作用尚不清楚。本研究利用大脑中动脉闭塞（MCAO）小鼠模型和氧葡萄糖剥夺（OGD）诱导的小胶质细胞模型来阐明SIRT7的机制。通过qPCR和免疫荧光评估小胶质细胞M1/M2极化，同时使用western blot和共免疫沉淀分析其潜在机制。我们的研究结果表明SIRT7在脑缺血损伤后显著下调。SIRT7过表达抑制ogd诱导的M1极化，而促进M2极化。在机制上，SIRT7介导烟酰胺磷酸核糖基转移酶（NAMPT）去琥珀酰化和随后的蛋白酶体降解，从而抑制M1极化并最终减轻脑损伤进展。这些发现为SIRT7在炎症反应中的调节作用提供了新的见解，并表明靶向SIRT7- nampt轴可能作为脑缺血相关疾病的一种有希望的治疗策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Brain Research Bulletin 医学-神经科学

CiteScore

6.90

自引率

2.60%

发文量

253

审稿时长

67 days

期刊介绍： The Brain Research Bulletin (BRB) aims to publish novel work that advances our knowledge of molecular and cellular mechanisms that underlie neural network properties associated with behavior, cognition and other brain functions during neurodevelopment and in the adult. Although clinical research is out of the Journal''s scope, the BRB also aims to publish translation research that provides insight into biological mechanisms and processes associated with neurodegeneration mechanisms, neurological diseases and neuropsychiatric disorders. The Journal is especially interested in research using novel methodologies, such as optogenetics, multielectrode array recordings and life imaging in wild-type and genetically-modified animal models, with the goal to advance our understanding of how neurons, glia and networks function in vivo.