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Comment
. 2018 Aug;10(8):e9369.
doi: 10.15252/emmm.201809369.

Microglia P2X4 receptors as pharmacological targets for demyelinating diseases

Francesco Di Virgilio  1 , Alba Clara Sarti  1
Affiliations
Comment

Microglia P2X4 receptors as pharmacological targets for demyelinating diseases

Francesco Di Virgilio et al. EMBO Mol Med. 2018 Aug.

Abstract

Pharmacological activation of the P2X4 receptor expressed by brain microglia may provide a novel avenue to promote remyelination and improve clinical symptoms in experimental autoimmune encephalomyelitis and potentially in multiple sclerosis.

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Figures

Figure 1
Figure 1. Modulation of the P2X4 receptor promotes pro‐ or anti‐inflammatory microglia differentiation
Inhibition of the P2X4 receptor (P2X4R) by the semi‐selective blocker TNP‐ATP (red arrow) drives microglia differentiation towards a pro‐inflammatory (M1) phenotype characterized by the enhanced release of pro‐inflammatory cytokines. On the contrary, P2X4R activation by ivermectin (IVM) (green arrow) drives differentiation towards an anti‐inflammatory phenotype characterized by trophic factor release and enhanced phagocytic activity. M1 microglia exacerbates axonal degeneration, while M2 microglia accelerates neuronal repair. The P2X4R is localized both on the plasma membrane and on the lysosomal membrane; therefore, the diverse responses coupled to its inhibition or activation, respectively, may depend on the differential stimulation of the P2X4R on these cellular compartments.
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Supplementary concepts