Watroba Mateusz, Szukiewicz Dariusz
Department of Biophysics and Human Physiology, Faculty of Health Sciences, Medical University of Warsaw, Warsaw, Poland.
Front Physiol. 2022 Aug 15;13:962769. doi: 10.3389/fphys.2022.962769. eCollection 2022.
Both basic pathomechanisms underlying Alzheimer's disease and some premises for stipulating a possible preventive role of some sirtuins, especially SIRT1 and SIRT3, protective against Alzheimer's disease-related pathology, are discussed in this article. Sirtuins can inhibit some processes that underlie Alzheimer's disease-related molecular pathology (e.g., neuroinflammation, neuroinflammation-related oxidative stress, A aggregate deposition, and neurofibrillary tangle formation), thus preventing many of those pathologic alterations at relatively early stages of their development. Subsequently, the authors discuss in details which mechanisms of sirtuin action may prevent the development of Alzheimer's disease, thus promoting brain homeostasis in the course of aging. In addition, a rationale for boosting sirtuin activity, both with allosteric activators and with NAD precursors, has been presented.
本文讨论了阿尔茨海默病的两种基本病理机制以及一些前提条件,这些前提条件表明某些沉默调节蛋白,特别是SIRT1和SIRT3,可能具有预防阿尔茨海默病相关病理的作用。沉默调节蛋白可以抑制一些与阿尔茨海默病相关分子病理学相关的过程(例如神经炎症、神经炎症相关的氧化应激、Aβ聚集沉积和神经原纤维缠结形成),从而在这些病理改变发展的相对早期阶段预防许多此类改变。随后,作者详细讨论了沉默调节蛋白的哪些作用机制可能预防阿尔茨海默病的发展,从而在衰老过程中促进脑内稳态。此外,还提出了使用变构激活剂和NAD前体增强沉默调节蛋白活性的理论依据。