She David T, Jo Dong-Gyu, Arumugam Thiruma V
Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117597, Singapore.
Neurobiology/Ageing Programme, Life Sciences Institute, National University of Singapore, Singapore, 117456, Singapore.
Transl Stroke Res. 2017 Jun 27. doi: 10.1007/s12975-017-0544-4.
Ischemic stroke is one of the leading causes of death worldwide. It is characterized by a sudden disruption of blood flow to the brain causing cell death and damage, which will lead to neurological impairments. In the current state, only one drug is approved to be used in clinical setting and new therapies that confer ischemic neuroprotection are desperately needed. Several targets and pathways have been indicated to be neuroprotective in ischemic stroke, among which the sirtuin family of nicotinamide adenine dinucleotide (NAD)-dependent deacetylases has emerged as important modulators of several processes in the normal physiology and pathological conditions such as stroke. Recent studies have identified some members of the sirtuin family are able to ameliorate the devastating consequences of ischemic stroke by conferring neuroprotection by means of reducing neuronal cell death, oxidative stress, and neuroinflammation whereas some sirtuins are found to be detrimental in the pathophysiology of ischemic stroke. This review summarizes implications of sirtuins in ischemic stroke and the experimental evidences that demonstrate the potential of sirtuin modulators as neuroprotective therapy for ischemic stroke.
缺血性中风是全球主要的死亡原因之一。其特征是脑部血液供应突然中断，导致细胞死亡和损伤，进而引发神经功能障碍。在目前的情况下，只有一种药物被批准用于临床，因此迫切需要能够提供缺血性神经保护作用的新疗法。已有多项靶点和信号通路被证明在缺血性中风中具有神经保护作用，其中烟酰胺腺嘌呤二核苷酸（NAD）依赖性去乙酰化酶的沉默调节蛋白家族已成为正常生理和病理状况（如中风）下多个过程的重要调节因子。最近的研究表明，沉默调节蛋白家族的一些成员能够通过减少神经元细胞死亡、氧化应激和神经炎症来提供神经保护作用，从而改善缺血性中风的严重后果，而另一些沉默调节蛋白则被发现在缺血性中风的病理生理过程中具有有害作用。本综述总结了沉默调节蛋白在缺血性中风中的意义，以及证明沉默调节蛋白调节剂作为缺血性中风神经保护疗法潜力的实验证据。
