Succinylation modification:a potential therapeutic target in stroke  

作　　者：Jie Lian Wenwu Liu Qin Hu Xiaohua Zhang 

机构地区：[1]Department of Neurosurgery,Ren Ji Hospital,Shanghai Jiao Tong University School of Medicine [2]Department of Diving and Hyperbaric Medicine,Naval Medical Center,Naval Medical University

出　　处：《Neural Regeneration Research》2024年第4期781-787,共7页中国神经再生研究（英文版）

基　　金：supported by the National Natural Science Foundation of China,No.82071283(to QH);the Natural Science Foundation of Shanghai,No.22ZR1437700(to QH)。

摘　　要：Stroke is a leading cause of mortality and disability worldwide.Ischemic cell death triggered by the compromised supply of blood oxygen and glucose is one of the major pathophysiology of strokeinduced brain injury.Impaired mitochondrial energy metabolism is observed minutes after stroke and is closely associated with the progression of neuropathology.Recently,a new type of posttranslational modification,known as lysine succinylation,has been recognized to play a significant role in mitochondrial energy metabolism after ischemia.However,the role of succinylation modification in cell metabolism after stroke and its regulation are not well understood.We aimed to review the effects of succinylation on energy metabolism,reactive oxygen species generation,and neuroinflammation,as well as Sirtuin 5 mediated desuccinylation after stroke.We also highlight the potential of targeting succinylation/desuccinylation as a promising strategy for the treatment of stroke.The succinylation level is dynamically regulated by the nonenzymatic or enzymatic transfer of a succinyl group to a protein on lysine residues and the removal of succinyl catalyzed by desuccinylases.Mounting evidence has suggested that succinylation can regulate the metabolic pathway through modulating the activity or stability of metabolic enzymes.Sirtuins,especially Sirtuin 5,are characterized for their desuccinylation activity and have been recognized as a critical regulator of metabolism through desuccinylating numerous metabolic enzymes.Imbalance between succinylation and desuccinylation has been implicated in the pathophysiology of stroke.Pharmacological agents that enhance the activity of Sirtuin 5 have been employed to promote desuccinylation and improve mitochondrial metabolism,and neuroprotective effects of these agents have been observed in experimental stroke studies.However,their therapeutic efficacy in stroke patients should be validated.

关 键 词：mitochondria metabolism NEUROPROTECTION sirtuin 5 STROKE succinylation modification 

分 类 号：R743.3[医药卫生—神经病学与精神病学]