Cannabinoid receptor 2: potential role in immunomodulation and neuroinflammation

Abstract

An accumulating body of evidence suggests that endocannabinoids and cannabinoid receptors type 1 and 2 (CB(1), CB(2)) play a significant role in physiologic and pathologic processes, including cognitive and immune functions. While the addictive properties of marijuana, an extract from the Cannabis plant, are well recognized, there is growing appreciation of the therapeutic potential of cannabinoids in multiple pathologic conditions involving chronic inflammation (inflammatory bowel disease, arthritis, autoimmune disorders, multiple sclerosis, HIV-1 infection, stroke, Alzheimer's disease to name a few), mainly mediated by CB(2) activation. Development of CB(2) agonists as therapeutic agents has been hampered by the complexity of their intracellular signaling, relative paucity of highly selective compounds and insufficient data regarding end effects in the target cells and organs. This review attempts to summarize recent advances in studies of CB(2) activation in the setting of neuroinflammation, immunomodulation and HIV-1 infection.

Figure 1

Multiple alignment and homology of human and mouse CB₁ and CB₂ receptors. Sequence alignment was performed using ClustalW tool (http://www.ebi.ac.uk/Tools/msa/clustalw2/). The following symbols denote the degree of conservation observed in each column: “*” means that the residues are identical in all sequences, “:” means that conserved substitutions have been observed, and “.” means that semi-conserved substitutions are observed.

Figure 2

Prototypical structures of natural and synthetic cannabinoids.