The complex modulation of lysosomal degradation pathways by cannabinoid receptors 1 and 2

Abstract

The two main receptors of the endocannabinoid system, cannabinoid receptors 1 (CB1R) and 2 (CB2R), were described in the early 1990s. Since then, different physiological functions have been revealed that are linked to the activity of these two G-protein-coupled receptors. CB1R and CB2R activities influence signal cascades, which are known to play a role in the regulation of the cellular "self-digestion" process called autophagy. A variety of these signaling pathways are integrated by the mammalian target of rapamycin complex 1 (mTORC1) that acts as an inhibitor of autophagy. Others, like AMP-activated protein kinase dependent signaling pathway, are able to bypass mTORC1 to modulate the autophagic activity directly. In the recent years, several scientific reports demonstrate an involvement of CB1R and CB2R signaling in the control of the autophagic activity in different paradigms. In this review, we summarize the recent literature on this topic, which is in part contradictory and therefore, it is of great importance to illuminate the results of the single reports in the physiological context of the model systems used in these studies. Utilizing CB1R and CB2R as pharmacological targets to modulate the autophagic activity is a promising strategy for the treatment of different patho-physiological conditions and disease.

Keywords: autophagy; cannabinoid receptor; lysosomal degradation.