Fig. 4

Crosstalk among several physiological and pathological processes leads to neuronal death after stroke. Misfolded proteins and paraproteins trigger ER stress and the UPR to activate the NLRP3 inflammasome and aggravate inflammatory responses; the NLRP3 inflammasome can also promote the UPR and ER stress. ROS accumulation, Ca²⁺ dyshomeostasis, and ER stress excessively activate autophagy. Autophagy normally inhibits the NLRP3 inflammasome but can induce NLRP3 inflammasome activation when it is excessive. The NLRP3 inflammasome can also act on autophagy. Lipid peroxide accumulation results in ferroptosis, and there is probably crosstalk between ferroptosis and NLRP3 inflammasome activation. ER stress, excessive autophagy, ferroptosis, and the NLRP3 inflammasome together form an LNAS