Extracellular vesicles as therapeutic modulators of neuroinflammation in Alzheimer's disease: a focus on signaling mechanisms

细胞外囊泡作为阿尔茨海默病神经炎症的治疗调节剂:聚焦信号传导机制

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Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of amyloid-beta (Aβ) plaques and tau tangles, which contribute significantly to neuroinflammation, a central driver of disease pathogenesis. The activation of microglia and astrocytes, coupled with the complex interactions between Aβ and tau pathologies and the innate immune response, leads to a cascade of inflammatory events. This process triggers the release of pro-inflammatory cytokines and chemokines, exacerbating neuronal damage and fostering a cycle of chronic inflammation that accelerates neurodegeneration. Key signaling pathways, such as nuclear factor-kappa B (NF-κB), Janus kinase/signal transducer and activator of transcription (JAK/STAT), mitogen-activated protein kinase (MAPK), and phosphoinositide 3-kinase/protein kinase B (PI3K/Akt), are involved in regulating the production of these inflammatory mediators, offering potential therapeutic targets for AD. Recently, extracellular vesicles (EVs) have emerged as a promising tool for AD therapy, due to their ability to cross the blood-brain barrier (BBB) and deliver therapeutic agents. Despite challenges in standardizing EV-based therapies and ensuring their safety, EVs offer a novel approach to modulating neuroinflammation and promoting neuroregeneration. This review aims to highlight the intricate relationship between neuroinflammation, signaling pathways, and the emerging role of EV-based therapeutics in advancing AD treatment strategies.

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