Figure 6
From: Cannabidiol induces autophagy via ERK1/2 activation in neural cells

available at smart.servier.com.
Schematic representation of the signaling pathway mediated by CBD in SH-SY5Y cells. At 10 µM, CBD activates autophagy, resulting in the accumulation of LC3-II and increased presence of LC3-positive puncta. AM 251, AM 630 and CPZ antagonists abrogated the observed LC3-II accumulation, thus implicating canonical cannabinoids (CB1 and CB2) and TRPV1 receptors in CBD-mediated autophagy. Additionally, CBD activated the ERK1/2 signaling cascade by increasing phosphorylation at Tyr204/Thr202 after 10 min of CBD treatment but suppressed the PI3K/AKT pathway by reducing AKT phosphorylation at S473. On the other hand, CBD treatment did not change AMPK phosphorylation at Thr172 or the phosphorylation levels of autophagy-related proteins ULK1 (Ser757) and p70S6K (Thr389). In conclusion, our findings suggest that CBD-induced autophagy activation is dependent on ULK1 and occurs in an mTORC1 independent-manner. Furthermore, the effects on the ERK1/2 and PI3K/AKT pathways, which regulate cell survival and proliferation, indicate that CBD could elicit neuroprotective actions. The illustration was produced using smart servier medical art vectors for publications and presentations licensed under the Creative Commons (CC BY 3.0)