Figure 2.

Direct (upper) and indirect (lower) pharmacological actions of GLP-1R agonists. (Upper) GLP-1 agonists act directly by stimulating the GLP-1R to induce multiple coordinated actions at the level of pancreatic islet cells, within the heart, gastrointestinal tract, on subsets of immune cells and within the brain. (Lower) Within the brain, that GLP-1R agonists appear to freely enter, activation of select GLP-1R signaling pathways instigates biological actions within the gastrointestinal tract, liver and adipose tissue.

Importantly, the activation of GLP-1R signaling cascades within the central and peripheral nervous systems appear to underpin the benefits of GLP-1R agonists described in preclinical animal models of AD, PD, stroke, ALS, Huntington's disease and, more recently TBI (adapted from Campbell and Drucker [82] and Salcedo et al., [75]).