P2Y1R-IGFBP2 signaling: new contributor to astrocyte-neuron communication.

In a recent article published in Nature Communications (Shigetomi et al Nat Commun 15(1):6525, 2024), Shigetomi et al. identified that upregulated astrocytic purinergic P2Y1 receptors (P2Y1R), acting via the downstream molecule, insulin-like growth factor binding protein 2 (IGFBP2), play a crucial role in neuronal hyperexcitability. In epilepsy and stroke models, P2Y1R-IGFBP2 signaling was found to mediate astrocyte-driven neuronal hyperexcitability and so is a new contributor to astrocyte-neuron communication. Thus, IGFBP2 could be an alternative target for treating the effects of upregulated P2Y1R activity in reactive astrocytes in neurological diseases.