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

作者：Jingnan Han, Xue Zhang, Longdan Kang, Jian Guan · 发表于：Journal of Neuroinflammation · 年份：2025 · DOI：10.1186/s12974-025-03443-1 · 被引用次数：20 · 研究领域：Extracellular vesicles in disease、MicroRNA in disease regulation、Circular RNAs in diseases

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...