Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Ooty, TN 643001, India.
Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Ooty, TN 643001, India.
Neurosci Biobehav Rev. 2024 Oct;165:105863. doi: 10.1016/j.neubiorev.2024.105863. Epub 2024 Aug 22.
The Wnt pathway stands out as a pivotal signal transduction pathway, operating through two distinct modes of signaling: the canonical/β-catenin pathway and the non-canonical pathway. Among these, the canonical pathway assumes a paramount role in various physiological and pathological processes within the human body. Particularly in the brain, Wnt exhibits involvement in fundamental physiological events including neuronal differentiation/survival, axonogenesis, neural stem cell regulation, synaptic plasticity, and cell cycle modulation. Notably, scientific evidence underscores the critical role of the Wnt pathway in the pathogenesis of Alzheimer's disease (AD), correlating with its involvement in key pathological features such as tau tangles, Amyloid-β plaques, synaptic dysfunction, oxidative stress, mitochondrial dysfunction, cognitive impairments, and disruption of the blood-brain barrier integrity. This review aims to comprehensively explore the involvement and significance of Wnt signaling in Alzheimer's. Furthermore, it delves into recent advancements in research on Wnt signaling, spanning from preclinical investigations to clinical trials.
Wnt 通路是一个关键的信号转导通路,通过两种不同的信号模式发挥作用:经典/β-连环蛋白途径和非经典途径。其中,经典途径在人体内的各种生理和病理过程中起着至关重要的作用。特别是在大脑中,Wnt 参与了包括神经元分化/存活、轴突发生、神经干细胞调节、突触可塑性和细胞周期调节在内的基本生理事件。值得注意的是,科学证据强调了 Wnt 途径在阿尔茨海默病(AD)发病机制中的关键作用,与它在关键病理特征中的参与相关,如 tau 缠结、β-淀粉样斑块、突触功能障碍、氧化应激、线粒体功能障碍、认知障碍和血脑屏障完整性的破坏。本综述旨在全面探讨 Wnt 信号在阿尔茨海默病中的作用和意义。此外,还深入探讨了 Wnt 信号研究的最新进展,从临床前研究到临床试验。