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

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, cou...

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Bibliographic Details
Main Authors: Jingnan Han, Xue Zhang, Longdan Kang, Jian Guan
Format: Article
Language:English
Published: BMC 2025-04-01
Series:Journal of Neuroinflammation
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Online Access:https://doi.org/10.1186/s12974-025-03443-1
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Summary: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.
ISSN:1742-2094