Anwar Mai M
Department of Biochemistry, National Organization for Drug Control and Research (NODCAR)/Egyptian Drug Authority (EDA), Cairo, Egypt.
Neuroscience Research Lab, Research Center for Translational Medicine (KUTTAM), Koç University, Istanbul, Turkey.
Cell Biochem Funct. 2022 Jan;40(1):17-27. doi: 10.1002/cbf.3673. Epub 2021 Oct 30.
Neurologists have highly observed a frequent increasing number of elderly patients with Alzheimer's disease (AD) without any relevant evidence of any genetic or known AD-linked predisposing factors in the past few years. Those patients are characterized by continuous and irreversible neuron cells loss along with declined cognitive functions. Numerous studies have suggested that the exaggerated release of reactive oxygen species (ROS) within the brain may develop late-onset neurodegenerative disorders, especially AD-neuroinflammatory type. However, the central nervous system is vitally linked with whole-brain chemical integrity and its related healthy state, the cascade by which ROS may result in AD's development has not been highly justified or even maintained. It is widely known that the brain consumes a vast amount of oxygen and is characterized by being rich in lipid polyunsaturated fatty acids content, explaining why it is a prone region to oxidative stress (OS) and ROS damage. The formed OS-AD cytoskeletal protein aggregates can be considered a main predisposing factor for amyloid-beta (Aβ) hallmarks precipitation. Herein, this review aims to provide a detailed information on how oxidative stress can play a pathogenic role in activating damage-associated molecular patterns (DAMPs)-related toll-like receptor-4 inflammatory (TLR-4) cascades resulting in the deposition of Aβ hallmarks in brain tissues ending with irreversible cognitive dysfunction. It also explains how microglia can be activated via ROS, which may significantly release several pro-inflammatory cascades ending with general brain atrophy. Furthermore, different types of suggested antioxidant therapies will be discussed to combat AD-related pathological disorders and hallmarks.
在过去几年中，神经科医生高度关注到老年阿尔茨海默病（AD）患者数量不断增加，且无任何遗传或已知的与AD相关的易感因素的相关证据。这些患者的特征是神经元细胞持续且不可逆地丧失，同时认知功能下降。大量研究表明，大脑中活性氧（ROS）的过度释放可能会引发迟发性神经退行性疾病，尤其是AD神经炎症型。然而，中枢神经系统与全脑化学完整性及其相关的健康状态密切相关，ROS导致AD发生的级联反应尚未得到充分证实甚至维持。众所周知，大脑消耗大量氧气，且富含脂质多不饱和脂肪酸，这解释了为什么它是一个易受氧化应激（OS）和ROS损伤的区域。形成的OS-AD细胞骨架蛋白聚集体可被认为是淀粉样β（Aβ）特征沉淀的主要易感因素。在此，本综述旨在提供详细信息，说明氧化应激如何在激活与损伤相关分子模式（DAMPs）相关的Toll样受体4炎症（TLR-4）级联反应中发挥致病作用，导致Aβ特征在脑组织中沉积，最终导致不可逆的认知功能障碍。它还解释了小胶质细胞如何通过ROS被激活，这可能会显著释放几种促炎级联反应，最终导致全脑萎缩。此外，还将讨论不同类型的建议抗氧化疗法，以对抗与AD相关的病理疾病和特征。
