Progress of Chinese Medicine in Regulating Microglial Polarization against Alzheimer's Disease

Abstract

Alzheimer's disease (AD), the predominant form of dementia, is a neurodegenerative disorder of the central nervous system (CNS) characterized by a subtle onset and a spectrum of cognitive and functional declines. The clinical manifestation of AD encompasses memory deficits, cognitive deterioration, and behavioral disturbances, culminating in a severe impairment of daily living skills. Despite its high prevalence, accounting for 60-70% of all dementia cases, there remains an absence of curative therapeutics. Microglia (MG), the resident immune cells of the CNS, exhibit a bifurcated role in AD pathogenesis. Functioning in a neuroprotective capacity, MGs express scavenger receptors, facilitating the clearance of β-amyloid protein (Aβ) and cellular debris. Conversely, aberrant activation of MGs can lead to the secretion of pro-inflammatory cytokines, thereby propagating neuroinflammatory responses that are detrimental to neuronal integrity. The dynamics of MG activation and the ensuing neuroinflammation are pivotal in the evolution of AD. Chinese medicine (CM), a treasure trove of traditional Chinese cultural practices, has demonstrated significant potential in the therapeutic management of AD. Over the past triennium, CM has garnered considerable research attention for its multifaceted approaches to AD, including the regulation of MG polarization. This review synthesizes current knowledge on the origins, polarization dynamics, and mechanistic interplay of MG with AD pathology. It further explores the nexus between MG polarization and cardinal pathological hallmarks of AD, such as Aβ plaque deposition, hyperphosphorylation of tau, synaptic plasticity impairments, neuroinflammation, and brain-gut-axis dysregulation. The review also encapsulates the therapeutic strategies of CM, which encompass monomers, formulae, and acupuncture. These strategies modulate MG polarization in the context of AD treatment, thereby providing a robust theoretical framework in which to conduct future investigative endeavors in both the clinical and preclinical realms.