Fig. 8: Scheme of inhibitory role of P2RX7 in astroglial autophagy induced by KA injection.
From: P2RX7-MAPK1/2-SP1 axis inhibits MTOR independent HSPB1-mediated astroglial autophagy
After SE, P2RX7 activation inhibited HSPB1 transactivation via MAPK1/2-mediated SP1-T739 phosphorylation. However, P2rx7 deletion or its antagonists impaired this inhibitory signaling pathway, which led to sustained HSPB1 expression and ER stress. Subsequently, ER stress activated PRKAA1/ULK1-mediated astroglial autophagy. Sustained HSPB1 expression also exerted AKT1/GSK3B-mediated SH3GLB1 accumulation, which triggered astroglial autophagy. Thus, P2RX7 regulated ER stress and autophagy by the fine-tuning of HSPB1 expression in astrocytes
