Advances in Immune Cell Interactions and Natural Compounds Therapeutic Strategies in Alzheimer's Disease.

As the global population ages, the incidence of Alzheimer's disease (AD) increases, burdening patients, families, and society. In recent years, microglia have been shown to interact with T cells, astrocytes, and other immune cells to form a complex immune microenvironment, which plays a damaging or protective role on neurons during the pathological process of AD. Herein, we review the interactions between microglia and other immune cells in the pathogenesis of AD and explore the potential of natural compounds as multi-targeted therapeutic strategies: (1) Balancing glial cell polarization status and ameliorating neuroinflammation by inhibiting core neuroinflammatory pathways such as NF-κB (nuclear factor kappa-B), MAPK, and NLRP3 inflammasome; (2) modulating the gut flora-brain axis function to inhibit central inflammation indirectly; (3) multi-targeted interventions for core AD pathology, including amyloid-beta (Aβ) clearance, tau phosphorylation, and synaptic plasticity. However, natural compounds still face clinical translation bottlenecks such as low bioavailability and poor blood-brain barrier permeability. Current studies have shown that nanocarrier systems and combination therapy strategies hold promise for addressing existing bottlenecks. However, systematic validation is still required for their clinical translation. This review systematically summarizes progress in the treatment of AD by regulating microglia and other immune cell interactions using natural compounds.