Fagerli Eric, Escobar Iris, Ferrier Fernando J, Jackson Charles W, Perez-Lao Efrain J, Perez-Pinzon Miguel A
Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL, United States.
Front Physiol. 2022 Jul 22;13:908689. doi: 10.3389/fphys.2022.908689. eCollection 2022.
Sirtuins are an evolutionarily conserved family of regulatory proteins that function in an NAD -dependent manner. The mammalian family of sirtuins is composed of seven histone deacetylase and ADP-ribosyltransferase proteins (SIRT1-SIRT7) that are found throughout the different cellular compartments of the cell. Sirtuins in the brain have received considerable attention in cognition due to their role in a plethora of metabolic and age-related diseases and their ability to induce neuroprotection. More recently, sirtuins have been shown to play a role in normal physiological cognitive function, and aberrant sirtuin function is seen in pathological cellular states. Sirtuins are believed to play a role in cognition through enhancing synaptic plasticity, influencing epigenetic regulation, and playing key roles in molecular pathways involved with oxidative stress affecting mitochondrial function. This review aims to discuss recent advances in the understanding of the role of mammalian sirtuins in cognitive function and the therapeutic potential of targeting sirtuins to ameliorate cognitive deficits in neurological disorders.
沉默调节蛋白是一类进化上保守的调节蛋白家族，以烟酰胺腺嘌呤二核苷酸（NAD）依赖的方式发挥作用。哺乳动物的沉默调节蛋白家族由七种组蛋白脱乙酰酶和ADP核糖基转移酶蛋白（SIRT1-SIRT7）组成，它们存在于细胞的不同细胞区室中。由于其在多种代谢和与年龄相关疾病中的作用以及诱导神经保护的能力，大脑中的沉默调节蛋白在认知方面受到了相当多的关注。最近，研究表明沉默调节蛋白在正常生理认知功能中发挥作用，并且在病理细胞状态下可观察到沉默调节蛋白功能异常。沉默调节蛋白被认为通过增强突触可塑性、影响表观遗传调控以及在涉及影响线粒体功能的氧化应激的分子途径中发挥关键作用来参与认知过程。本综述旨在讨论在理解哺乳动物沉默调节蛋白在认知功能中的作用以及靶向沉默调节蛋白以改善神经疾病中认知缺陷的治疗潜力方面的最新进展。
