![]() |
Figure 3: Summary of the principal signalling pathways through which glucagon-like peptide-1 receptor activation promotes neuronal cell survival. Stimulation of the GLP-1R on the surface of neuronal calls activates protective signalling pathways, downstream of phosphoinoside kinase 3 (PiK3) and adenylate cyclase (AC) [63]. Activation of protein kinase A (PKA) leads to modulation of prosurvival gene expression via the extracellular signal-related kinase/ mitogen-activated protein kinase (ERK/MAPK) and cAMP response element-binding protein (CREB) pathways [52,56]. Similarly, protein kinase C (PKC) and Akt signal through ERK/ MAPK and mTOR (mammalian target of rapamycin), respectively, to promote neuronal cell proliferation and modulate levels of apoptotic gene expression (decreased Bax and Caspase-3; increased Bcl-2). |