Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Department of Neurology, School of Medicine, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Cell Stress Chaperones. 2021 Nov;26(6):871-887. doi: 10.1007/s12192-021-01231-3. Epub 2021 Aug 13.
Among the long list of age-related complications, Alzheimer's disease (AD) has the most dreadful impact on the quality of life due to its devastating effects on memory and cognitive abilities. Although a plausible correlation between the phosphatidylinositol 3-kinase (PI3K) signaling and different processes involved in neurodegeneration has been evidenced, few articles reviewed the task. The current review aims to unravel the mechanisms by which the PI3K pathway plays pro-survival roles in normal conditions, and also to discuss the original data obtained from international research laboratories on this topic. Responses to questions on how alterations of the PI3K/Akt signaling pathway affect Tau phosphorylation and the amyloid cascade are given. In addition, we provide a general overview of the association between oxidative stress, neuroinflammation, alterations of insulin signaling, and altered autophagy with aberrant activation of this axis in the AD brain. The last section provides a special focus on the therapeutic possibility of the PI3K/Akt/mTOR modulators, either categorized as chemicals or herbals, in AD. In conclusion, determining the correct timing for the administration of the drugs seems to be one of the most important factors in the success of these agents. Also, the role of the PI3K/Akt signaling axis in the progression or repression of AD widely depends on the context of the cells; generally speaking, while PI3K/Akt activation in neurons and neural stem cells is favorable, its activation in microglia cells may be harmful.
在与年龄相关的众多并发症中，阿尔茨海默病（AD）对生活质量的影响最为可怕，因为它对记忆和认知能力的破坏性影响。尽管已经有证据表明磷脂酰肌醇 3-激酶（PI3K）信号与神经退行性过程中涉及的不同过程之间存在合理的相关性，但很少有文章对此进行综述。本综述旨在揭示 PI3K 途径在正常情况下发挥生存作用的机制，并讨论国际研究实验室在这一主题上获得的原始数据。回答了 PI3K/Akt 信号通路的改变如何影响 Tau 磷酸化和淀粉样蛋白级联反应的问题。此外，我们还提供了关于氧化应激、神经炎症、胰岛素信号改变和自噬改变与 AD 大脑中该轴的异常激活之间的一般概述。最后一部分特别关注 PI3K/Akt/mTOR 调节剂的治疗可能性，这些调节剂分为化学物质和草药，用于 AD。总之，确定药物给药的正确时间似乎是这些药物成功的最重要因素之一。此外，PI3K/Akt 信号轴在 AD 的进展或抑制中的作用在很大程度上取决于细胞的上下文；一般来说，虽然神经元和神经干细胞中 PI3K/Akt 的激活是有利的，但小胶质细胞中其激活可能是有害的。
