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中医药在阿尔茨海默病治疗中的应用:聚焦Wnt/β-连环蛋白信号通路

Application of Traditional Chinese Medicine in Alzheimer's Disease Treatment: A Focus on the Wnt/[Formula: see text]-Catenin Pathway.

作者信息

Ying Chunmiao, He Yuxuan, Guo Yingshu, Fan Feiyan, Wang Boqiao, Gao Jing, Li Yiwen, Zhang Yunke

机构信息

Department of Encephalopathy, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China.

Department of the First Clinical Medical School, Henan University of Chinese Medicine, Zhengzhou, China.

出版信息

Am J Chin Med. 2025;53(6):1641-1683. doi: 10.1142/S0192415X25500624. Epub 2025 Aug 1.

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder primarily characterized by cognitive decline. Its etiology and pathogenesis are complex and multifactorial, with neurotoxicity induced by the abnormal aggregation of amyloid-beta (A[Formula: see text]) protein widely recognized as a central pathological hallmark. Current pharmacological treatments provide only limited symptomatic relief and are often associated with dose-dependent adverse effects. In contrast, Traditional Chinese Medicine (TCM) has garnered growing attention due to its distinctive therapeutic profile, and in particular, its multi-target and multi-pathway synergistic mechanisms. The Wnt/[Formula: see text]-catenin signaling pathway plays a crucial role in intracellular signal transduction and is closely associated with several key pathological processes involved in AD. This review provides a comprehensive analysis of the molecular interplay between the Wnt/[Formula: see text]-catenin signaling pathway and the pathogenesis of AD, as well as a specific focus on how natural compounds, herbal monomers, and classical TCM formulations modulate this pathway. Accumulating evidence suggests that TCM exerts neuroprotective effects by regulating Wnt/[Formula: see text]-catenin signaling to thereby suppress A[Formula: see text] deposition, preserve synaptic structure and tissue homeostasis, modulate cell proliferation and apoptosis, and maintain metabolic and redox homeostasis. Additionally, the review discusses key challenges, such as improving blood-brain barrier permeability and enhancing bioavailability, and outlines future directions involving advanced delivery systems and optimized administration routes. These insights provide a robust scientific foundation for the development of Wnt/[Formula: see text]-catenin-targeted therapies and highlight the potential of TCM in the clinical treatment of AD.

摘要

阿尔茨海默病(AD)是一种主要以认知功能衰退为特征的进行性神经退行性疾病。其病因和发病机制复杂且具有多因素性,由β-淀粉样蛋白(Aβ)异常聚集诱导的神经毒性被广泛认为是核心病理标志。目前的药物治疗仅提供有限的症状缓解,且常伴有剂量依赖性不良反应。相比之下,传统中医(TCM)因其独特的治疗特点,尤其是其多靶点和多途径协同机制而受到越来越多的关注。Wnt/β-连环蛋白信号通路在细胞内信号转导中起关键作用,并且与AD涉及的几个关键病理过程密切相关。本综述全面分析了Wnt/β-连环蛋白信号通路与AD发病机制之间的分子相互作用,特别关注天然化合物、草药单体和经典中药配方如何调节该通路。越来越多的证据表明,中药通过调节Wnt/β-连环蛋白信号发挥神经保护作用,从而抑制Aβ沉积、维持突触结构和组织稳态、调节细胞增殖和凋亡,并维持代谢和氧化还原稳态。此外,该综述讨论了关键挑战,如提高血脑屏障通透性和增强生物利用度,并概述了涉及先进递送系统和优化给药途径的未来方向。这些见解为开发靶向Wnt/β-连环蛋白的疗法提供了坚实的科学基础,并突出了中药在AD临床治疗中的潜力。

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