Fig. 9

Diagram of the proposed mechanistic signaling pathway. Although cerebral ischemia leads to autophagic activation, it reduces the DOR level and inhibits AMPK activity, leading to endogenous defense exhaustion and eventually neuronal death (left). However, DOR activation by DADLE triggers AMPK/mTOR/ULK1 signaling, further enhancing neuronal autophagy and alleviating autophagic flux dysfunction to ameliorate ischemic neuronal survival (right)