Fig. 8.

Proposed schematic mechanisms of adropin-mediated neuroprotection in ischemic stroke.Left: Stroke induces eNOS phosphorylation (p-eNOS) to release nitric oxide (NO), together with upregulation of gp91phox-containing NADPH oxidase (NOX2) to produce superoxide (O2^-.). The reaction between NO and O2^-. forms peroxynitrite (ONOO⁻), resulting in a decrease in NO bioavailability and MMP-9 activation through the S-nitrosylation of MMP-9 pro-domain “cysteine switch” mechanism, which ultimately leads to endothelial dysfunction, disruption of the blood-brain barrier (BBB), and brain damage. Right: Treatment with adropin or adropin overexpression can induce a higher level of eNOS phosphorylation-derived NO generation (double red arrow) and inhibit NOX2 from producing O2^-. in ischemic stroke, which decreases the ONOO⁻ formation. These effects may finally improve endothelial function and inhibit MMP-9 activity resulting in reduced BBB damage and neuroprotection. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)