title: Systems biology analysis of the endocannabinoid system reveals a scale-free network with distinct roles for anandamide and 2-arachidonoylglycerol.
abstract: We represented the endocannabinoid system (ECS) as a biological network, where ECS molecules are the nodes (123) and their interactions the links (189). ECS network follows a scale-free topology, which confers robustness against random damage, easy navigability, and controllability. Network topological parameters, such as clustering coefficient (i.e., how the nodes form clusters) of 0.0009, network diameter (the longest shortest path among all pairs of nodes) of 12, averaged number of neighbors (the mean number of connections per node) of 3.073, and characteristic path length (the expected distance between two connected nodes) of 4.715, suggested that molecular messages are transferred through the ECS network quickly and specifically. Interestingly, ∼75% of nodes are located on, or are active at the level of, the cell membrane. The hubs of ECS network are anandamide (AEA) and 2-arachidonoylglycerol (2-AG), which have also the highest value of betweeness centrality, and their removal causes network collapse into multiple disconnected components. Importantly, AEA is a ubiquitous player while 2-AG plays more restricted actions. Instead, the product of their degradation, arachidonic acid, and their hydrolyzing enzyme, fatty acid amide hydrolase, FAAH, have a marginal impact on ECS network, indeed their removal did not significantly affect its topology.
authors.affiliation: 1 Department of Biomedical Sciences, University of Teramo , Teramo, Italy .
authors.forename: Nicola
authors.initials: N
authors.lastname: Bernabò
authors.forename: Barbara
authors.initials: B
authors.lastname: Barboni
authors.forename: Mauro
authors.initials: M
authors.lastname: Maccarrone
mesh_terms: D001095:Arachidonic Acids / Q000502:physiology*; D003198:Computer Simulation; D063388:Endocannabinoids / Q000502:physiology*; D005989:Glycerides / Q000502:physiology*; D006801:Humans; D053858:Metabolic Networks and Pathways; D008954:Models, Biological; D053284:Polyunsaturated Alkamides; D015398:Signal Transduction; D049490:Systems Biology
chemical_list: D001095:Arachidonic Acids; D063388:Endocannabinoids; D005989:Glycerides; D053284:Polyunsaturated Alkamides; C094503:glyceryl 2-arachidonate; C078814:anandamide