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image of Targeting Microglial Phagocytosis for Alzheimer's Disease Management: Natural, Pharmacological, Nanoparticle, and Gene Therapy Approaches

Abstract

Persistent swelling in the brain, internal tau bundles, and external Amyloid-Beta (Aβ) deposits are characteristics of Alzheimer's Disease (AD), an ongoing neurodegenerative illness. Microglia are the main immune cells in the CNS (Central Nervous System). They keep the brain stable by keeping an eye on the immune system and removing apoptotic cells and protein clusters through a process called phagocytosis. However, in AD, microglia exhibit dysregulated phagocytic activity, resulting in either insufficient Aβ clearance or exacerbated inflammatory responses, both of which contribute to neurodegeneration. This review examines key molecular pathways, such as those mediated by TREM2 (Triggering Receptor Expressed on Myeloid cells), APOE (Apolipoprotein E), and CD33 (Cluster of Differentiation), that govern microglial activation and influence their neuroprotective or neurotoxic functions. We further explore therapeutic strategies to modulate microglial phagocytosis, pharmacological agents (such as minocycline, pioglitazone, rifampicin, .), some natural agents, gene-editing tools, and nanomedicine, which aim to optimise microglial response and reduce the neuroinflammatory burden in AD. Despite promising advances, challenges persist in achieving targeted, effective modulation of microglial function due to microglial heterogeneity, limited model fidelity, and potential off-target effects. This review underscores the importance of refining microglia-targeted interventions and developing combinatory approaches that enhance microglial homeostasis to mitigate AD pathology and progression.

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2025-07-09
2025-09-30

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Targeting Microglial Phagocytosis for Alzheimer's Disease Management: Natural, Pharmacological, Nanoparticle, and Gene Therapy Approaches
Bentham Science Publishers ; https://doi.org/10.2174/0118715273378092250623064748
/content/journals/cnsnddt/10.2174/0118715273378092250623064748
/content/journals/cnsnddt/10.2174/0118715273378092250623064748
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  • Article Type:     Review Article
Keywords: natural agents ; microglial phagocytosis ; Alzheimer’s disease ; gene therapy ; neurodegenerative disease ; gene

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