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. 2022 Mar 15;13:844697. doi: 10.3389/fneur.2022.844697

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Copyright © 2022 Yang, Qiang, Li, Feng, Wei and Hölscher.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Proposed mechanisms of neuroprotective efficacy exerted by GLP-1 and GLP-1RAs against stroke in animals. Effects of GLP-1 and GLP-1RAs are mediated by binding to a specific, seven-transmembrane GLP-1R which is positively coupled to the adenylyl cyclase (AC) system. GLP-1 and GLP-1RAs acts directly by the cAMP/PKA signal pathway to facilitate gene transcription, synapse growth and repair, cell growth, and regeneration. The Gβγ dimer stimulates the PI3K, which then activates PKB/AKT pathway to inhibit apoptosis. In addition, GLP-1 and GLP-1 RAs play a role through reduction of blood-brain barrier leakage and neurotransmitter transmission among synapses as well.