Schematic drawing of the major neuroprotective signaling pathways regulated by ghrelin and GHS

A schematic drawing of the major neuroprotective signaling pathways regulated by ghrelin and GHS. The canonical pathway of ghrelin and GHS activities involves their binding to the GHS-R1a receptor. GHS-R1a activation results in the hydroxylation of phosphatidylinositol 4,5-bisphosphate (PIP2) to generate the secondary messengers inositol 1,4,5-triphosphate (IP3) and diacylglycerol (DAG), which lead to mobilization of intracellular calcium (Ca2+) stores and to protein kinase C (PKC) activation. PKC mediates different cellular responses, including the stimulation of mitogen-activated protein kinases (MAPKs), and the protein inositol 3 kinase (PI3K)/Akt pathway. The alternative pathways of ghrelin and GHS activities include the binding and activation of CD36 or other unknown receptors, which stimulates the activation of MAPKs and Akt, inhibits the generation of reactive oxygen species (ROS) and reduce the activation of BAX, a pro-apoptotic molecule, suppressing apoptosis and improving cell survival. Ghrelin and GHS also attenuate neuroinflammation involving the NLRP3 inflammasome signaling pathway and pyroptosis. Created in Biorender.com.

Publication

Potential Applications for Growth Hormone Secretagogues Treatment of Amyotrophic Lateral Sclerosis (2023) Ramona Meanti, et al. Curr Neuropharmacol. 2023 Sep 25;21(12):NA. Figure: F1. Homo sapiens

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