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

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.

Keywords: Alzheimer’s Disease; Bioactive Components from Natural Products; Chinese Herbal Formulations; Traditional Chinese Medicine; Wnt/[Formula: see text]-Catenin Signaling Pathway.