Razick Daniel I, Akhtar Muzammil, Wen Jimmy, Alam Meraj, Dean Nabeal, Karabala Muhammad, Ansari Ubaid, Ansari Zaid, Tabaie Ethan, Siddiqui Shakeel
Surgery, California Northstate University College of Medicine, Elk Grove, USA.
Physical Medicine and Rehabilitation, California Northstate University College of Medicine, Elk Grove, USA.
Cureus. 2023 Jun 15;15(6):e40463. doi: 10.7759/cureus.40463. eCollection 2023 Jun.
Sirtuins (SIRT) are a class of histone deacetylases that regulate important metabolic pathways and play a role in several disease processes. Of the seven mammalian homologs currently identified, sirtuin 1 (SIRT1) is the best understood and most studied. It has been associated with several neurodegenerative diseases and cancers. As such, it has been further investigated as a therapeutic target in the treatment of disorders such as Parkinson's disease (PD), Huntington's disease (HD), and Alzheimer's disease (AD). SIRT1 deacetylates histones such as H1 lysine 26, H3 lysine 9, H3 lysine 56, and H4 lysine 16 to regulate chromatin remodeling and gene transcription. The homolog has also been observed to express contradictory responses to tumor suppression and tumor promotion. Studies have shown that SIRT1 may have anti-inflammatory properties by inhibiting the effects of NF-κB, as well as stimulating upregulation of autophagy. The SIRT1 activators resveratrol and cilostazol have been shown to improve Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) scores in AD patients. In this review, we aim to explore the various roles of SIRT1 with regard to neuroprotection and neurodegeneration.
沉默调节蛋白（SIRT）是一类组蛋白去乙酰化酶，可调节重要的代谢途径，并在多种疾病进程中发挥作用。在目前已鉴定出的七种哺乳动物同源物中，沉默调节蛋白1（SIRT1）是研究最深入、了解最透彻的。它与多种神经退行性疾病和癌症有关。因此，它作为治疗帕金森病（PD）、亨廷顿病（HD）和阿尔茨海默病（AD）等疾病的治疗靶点，受到了进一步研究。SIRT1使组蛋白如H1赖氨酸26、H3赖氨酸9、H3赖氨酸56和H4赖氨酸16去乙酰化，以调节染色质重塑和基因转录。人们还观察到该同源物对肿瘤抑制和肿瘤促进表现出矛盾的反应。研究表明，SIRT1可能通过抑制核因子κB（NF-κB）的作用以及刺激自噬上调而具有抗炎特性。已证明SIRT1激活剂白藜芦醇和西洛他唑可改善AD患者的阿尔茨海默病评估量表认知分量表（ADAS-Cog）评分。在这篇综述中，我们旨在探讨SIRT1在神经保护和神经退行性变方面的各种作用。
