Novel Therapeutic Strategies for Ischemic Stroke: Recent Insights into Autophagy

Figure 4

Manipulation of autophagy in brain microvascular endothelial cells after ischemic stroke. Circ-FoxO3 inhibits mTORC1 activity mainly by sequestering mTOR and E2F1, thus promoting autophagy to clear cytotoxic aggregates for improving BBB integrity [130]. Netrin-1 ameliorates BBB impairment secondary to ischemic stroke by activating PI3K-mediated autophagy depending on UNC5H2 receptor [129]. LncRNA Malat1 protects brain microvascular endothelial cells (BMECs) against ischemic injury by sponging miR-26b and upregulating ULK2 expression, thereby promoting BMEC autophagy [131]. Rapamycin and lithium carbonate pretreatments improve BBB integrity after ischemic stroke through induction of mTOR-dependent and mTOR-independent autophagy, respectively [127]. YZ001, a new σ-1R agonist, enhances pericyte survival via inhibition of autophagy in ischemic stroke [136].