BACKGROUND:Astrocytes play a crucial role in Alzheimer's disease (AD) pathogenesis, contributing to inflammation, amyloid plaque formation, and disease progression, making them promising therapeutic targets. Despite extensive research, the mechanisms underlying astrocytic dysfunction in AD and their modulation by phytochemicals remain incompletely understood, representing a critical gap in current knowledge.
PURPOSE:This review aims to elucidate the pathological mechanisms involving astrocytes in AD and evaluate the therapeutic potential of phytochemicals in modulating astrocytic activity.
METHODS:We systematically analysed recent studies on astrocytic activation, target receptors, and signalling pathways in AD and their regulation by phytochemicals. The studies were identified through searches of databases including PubMed, Web of Science, ScienceDirect, and Google Scholar.
RESULTS:Our findings reveal that abnormal activation of astrocytic receptors and downstream signaling pathways, such as RAGE/NF-κB, ERK/c-fos/NFATc1, AKT/Nrf2/NF-κB, and PI3K/Akt/GSK-3β, disrupt immune homeostasis in AD models. Phytochemicals, including tanshinone IIA, honokiol, aucubin, cornuside, luteolin, naringenin, daphnetin, and gelsemine, show promising effects in delaying AD progression. These effects are mediated through multiple mechanisms, such as inhibiting pro-inflammatory pathways, enhancing anti-inflammatory responses, promoting Aβ clearance, stimulating synaptogenesis, regulating neurotrophic factors, and reducing oxidative stress. These findings highlight the pivotal role of astrocytes in AD pathophysiology and the potential of phytochemicals to modulate astrocytic dysfunction.
CONCLUSIONS:By providing a comprehensive overview of astrocytic mechanisms and therapeutic interventions, this review offers a theoretical foundation for developing phytochemical-based strategies in AD therapy and underscores the need for further preclinical and clinical investigations to translate these findings into practical treatments.