当前位置: X-MOL 学术J. Alzheimer’s Dis. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Deciphering Alzheimer’s Disease Pathogenic Pathway: Role of Chronic Brain Hypoperfusion on p-Tau and mTOR
Journal of Alzheimer’s Disease ( IF 4 ) Pub Date : 2021-01-11 , DOI: 10.3233/jad-201165
Jack C de la Torre 1, 2
Affiliation  

Abstract

This review examines new biomolecular findings that lend support to the hemodynamic role played by chronic brain hypoperfusion (CBH) in driving a pathway to Alzheimer’s disease (AD). CBH is a common clinical feature of AD and the current topic of intense investigation in AD models. CBH is also the basis for the vascular hypothesis of AD which we originally proposed in 1993. New biomolecular findings reveal the interplay of CBH in increasing tau phosphorylation (p-Tau) in the hippocampus and cortex of AD mice, damaging fast axonal transport, increasing signaling of mammalian target of rapamycin (mTOR), impairing learning-memory function, and promoting the formation of neurofibrillary tangles, a neuropathologic hallmark of AD. These pathologic elements have been singularly linked with neurodegeneration and AD but their abnormal, collective participation during brain aging have not been fully examined. The format for this review will provide a consolidated analysis of each pathologic phase contributing to cognitive decline and AD onset, summarized in nine chronological steps. These steps galvanize each factor’s active participation and contribution in constructing a biomolecular pathway to AD onset generated by CBH.



中文翻译:

解读阿尔茨海默病的致病途径:慢性脑灌注不足对 p-Tau 和 mTOR 的作用

摘要

本综述检查了新的生物分子发现,这些发现支持慢性脑灌注不足 (CBH) 在驱动阿尔茨海默病 (AD) 通路中所起的血流动力学作用。CBH 是 AD 的常见临床特征,也是当前 AD 模型中深入研究的主题。CBH 也是我们在 1993 年最初提出的 AD 血管假说的基础。新的生物分子研究结果揭示了 CBH 在增加 AD 小鼠海马和皮层中 tau 磷酸化 (p-Tau)、破坏快速轴突运输、增加哺乳动物雷帕霉素靶蛋白 (mTOR) 的信号传导,损害学习记忆功能,并促进神经原纤维缠结的形成,这是 AD 的神经病理学标志。这些病理因素与神经变性和 AD 有着奇异的联系,但它们的异常、大脑衰老过程中的集体参与尚未得到充分研究。本综述的格式将提供对导致认知能力下降和 AD 发作的每个病理阶段的综合分析,总结为九个时间顺序。这些步骤激发了每个因素在构建由 CBH 产生的 AD 发病的生物分子途径中的积极参与和贡献。

更新日期:2021-01-12
down
wechat
bug