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Chemokine receptor CX3CR1 modulates microglial activity through Tau and amyloid-β interactions in Alzheimer's disease.

Created on 22 Aug 2026

Authors

Vaishnavi Ananathanarayana, Riddhi Upadhyay, Gouri H Illanad, Deena Krishnan, Neha P Bochageri, Murugan Sevanan, Zabin Bagewadi, R Sivasamy, Subashchandrabose Chinnathambi

Published in

Advances in immunology. Volume 171. Pages 83-108. Epub Dec 01, 2025.

Abstract

Alzheimer's disease is one of the most prevalent forms of dementia characterized by neurocognitive decline. Key proteins involved in the progression of disease is amyloid-β and Tau. Abnormal accumulation of amyloid-β senile plaques and Tau neurofibrillary tangles are characteristic features of AD which drives synaptic dysfunction and leads to cognitive decline. Recent studies emphasizes the importance of G-protein coupled receptors in regulating microglial cells and has diverse functions in modulating AD, particularly in the clearance of these pathological proteins. Among these GPCRs, the chemokine receptor CX3CR1 has a critical role at the intersection of pathological proteins and microglial signalling. CX3CR1 receptor mediated signalling influences interaction between microglia and neuron mediating microglial uptake and processing of Aβ and Tau. Aging is also one of the risk factors of AD which alters CX3CR1 signalling, thereby exacerbating disease progression. This review highlights the multifaceted role of CX3CR1 in Tau and Aβ pathology and outlines its signalling mechanisms. Importantly, this review emphasizes the therapeutic potential of targeting the CX3CL1-CX3CR1 axis and involved in protein clearance and reduces neuroinflammation preserving synaptic function, offering a promising way to prevent AD.

PMID:
42629135
Bibliographic data and abstract were imported from PubMed on 22 Aug 2026.

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