College of Pharmacy, Taif University, Taif, 21974, Saudi Arabia.
College of Pharmacy, Mohammad Al-Mana College for Health Sciences, Safa, Dammam, 34222, Saudi Arabia.
Mol Neurobiol. 2020 Jan;57(1):302-314. doi: 10.1007/s12035-019-01700-y. Epub 2019 Jul 20.
It has been well established in recent research that there is a strong correlation between metabolic syndrome (MetS) and Alzheimer's disease (AD). However, the knowledge of exact mechanistic behind this association remains elusive. It has been reported in recent studies that inflammation and hypercoagulation are pivotal to the pathophysiology of MetS-induced AD. It is rather captivating that aberrant Wnt signaling pathway has been found to be implicated in each of the four conditions, i.e., inflammation, hypercoagulation, MetS, and AD. Deregulation of Wnt signaling has been affiliated with numerous brain pathologies, including Alzheimer's disease and insulin resistance. In recent past, it has been proposed that the Wnt pathway can act as a central integrator of metabolic signals from peripheral organs to the brain, which would constitute a unique character for Wnt signaling in glucose metabolism. The review educates in what way distinct components of Wnt signaling impact effector mediators of inflammation, hypercoagulation, which in turn decelerate the progression of AD in MetS. Furthermore, components of Wnt signaling, namely, Wnt3a and GSK-3β, interlink MetS and AD. The review opines a contemporary hypothesis that Wnt signaling is implicated in the pathogenesis of MetS-induced AD via impacting inflammation and coagulation. Hence, targeting Wnt signaling could be a novel approach to halt the progression of MetS-linked AD.
近年来的研究已经充分证实，代谢综合征（MetS）与阿尔茨海默病（AD）之间存在很强的相关性。然而，这种关联的确切机制仍然难以捉摸。最近的研究报告表明，炎症和高凝状态是代谢综合征引起的 AD 病理生理学的关键。令人着迷的是，异常的 Wnt 信号通路被发现与四种情况之一有关，即炎症、高凝状态、MetS 和 AD。Wnt 信号的失调与许多脑部疾病有关，包括阿尔茨海默病和胰岛素抵抗。最近有人提出，Wnt 途径可以作为外周器官代谢信号向大脑传递的中心整合器，这将构成 Wnt 信号在葡萄糖代谢中的独特特征。该综述阐述了 Wnt 信号的不同成分如何影响炎症、高凝的效应介质，从而减缓 MetS 中 AD 的进展。此外，Wnt 信号的成分，即 Wnt3a 和 GSK-3β，将 MetS 和 AD 联系起来。该综述提出了一个当代假说，即 Wnt 信号通过影响炎症和凝血参与代谢综合征引起的 AD 的发病机制。因此，靶向 Wnt 信号可能是阻止 MetS 相关 AD 进展的一种新方法。
