Chemokine Receptors and Their Ligands

Ligands Chemokine subfamily Alpha Beta Gamma Delta

Cysteine motif CXC CC C CX3C

Number of chemokine ligands 13 17 11

Receptors Number of receptors 6 10 1 1

Receptor nomenclature CXCR1 CCR1 XCR1 CX3CR1

through 6 through 10

C = cysteine residue. X = any amino acid residue.

Chemokine receptors are expressed on neurons, microglia, and glia and may modulate various aspects of neuroinflammation and neurodegeneration.191 For example, neuronal presynaptic chemokine receptors have been shown to inhibit glutamate release and may thereby modulate excitotoxicity.192 Additional effects of chemokines directly on neurons may also play a role in disease progression. In AD, the chemokines IP-10 and Gro-a are elevated. Upon binding to CXCR3 and CXCR2, their respective receptors in neurons, they activate intracellular signaling pathways that may cause t-hyperphosphorylation.193 Chemokine release in the CNS likely also plays a more traditional inflammatory role as lymphocytes are able to penetrate the CNS in response to chemotactic agents released from activated astrocytes and glia, thereby amplifying the inflammatory response. Indeed, neuroinflammation is recognized as a significant component of neurodegenerative disease pathology.

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