Khan Heena, Tiwari Palak, Kaur Amarjot, Singh Thakur Gurjeet
Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, India.
Mol Neurobiol. 2021 Aug;58(8):3903-3917. doi: 10.1007/s12035-021-02387-w. Epub 2021 Apr 20.
Sirtuins are the class III of histone deacetylases that depend on nicotinamide adenine dinucleotide for their activity. Sirtuins can influence the progression of neurodegenerative disorders by switching between deacetylation and acetylation processes. Histone acetylation occurs when acetyl groups are added to lysine residues on the N-terminal part of histone proteins. Deacetylation, on the other hand, results in the removal of acetyl groups. Pharmacological modulation of sirtuin activity has been shown to influence various neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, Huntington's disease, stroke, and amyotrophic lateral sclerosis. In this review, mechanistic perspective of sirtuins has been discussed in anti-inflammatory, antiapoptotic, and neuroprotective effects in various disorders. We have discussed the structure, neurobiology, and physiology of sirtuins in neurodegenerative disease. Recent preclinical and clinical studies and their outcome have also been elucidated. The aim of this review is to fill in the gaps in our understanding of sirtuins' role in histone acetylation and deacetylation in all neurodegenerative diseases. Here, we emphasized on reviewing all the studies carried out in various labs depicting the role of sirtuin modulators in neuroprotection and highlighted the ideas that can be considered for future perspectives. Taken together, sirtuins may serve as a promising therapeutic target for the treatment of neurodegenerative disorders.
沉默调节蛋白是Ⅲ类组蛋白去乙酰化酶，其活性依赖于烟酰胺腺嘌呤二核苷酸。沉默调节蛋白可通过在去乙酰化和乙酰化过程之间转换来影响神经退行性疾病的进展。组蛋白乙酰化发生在乙酰基添加到组蛋白蛋白质N端的赖氨酸残基上时。另一方面，去乙酰化导致乙酰基的去除。已证明对沉默调节蛋白活性进行药理学调节可影响包括阿尔茨海默病、帕金森病、亨廷顿病、中风和肌萎缩侧索硬化症在内的各种神经退行性疾病。在这篇综述中，讨论了沉默调节蛋白在各种疾病中的抗炎、抗凋亡和神经保护作用的机制观点。我们讨论了沉默调节蛋白在神经退行性疾病中的结构、神经生物学和生理学。还阐明了最近的临床前和临床研究及其结果。这篇综述的目的是填补我们对沉默调节蛋白在所有神经退行性疾病的组蛋白乙酰化和去乙酰化中作用理解上的空白。在这里，我们着重回顾了各个实验室进行的所有研究，这些研究描述了沉默调节蛋白调节剂在神经保护中的作用，并强调了可用于未来展望的观点。综上所述，沉默调节蛋白可能是治疗神经退行性疾病的一个有前景的治疗靶点。
