Endocannabinoid system as a drug target - Savinainen

Research group

Bioactive lipids, such as eicosanoids, endocannabinoids and lysophospholipids are endogenous signaling molecules with wide spectrum of (patho)physiological functions in regulating cellular activity. Typically, these lipophilic messengers are produced "on demand" from cell membrane precursors and are released by specific enzymatic activity in response to e.g. extracellular stimuli. The levels and signaling function of these lipid mediators, such as endocannabinoids, are tightly regulated by metabolic enzymes, many of which still remain poorly characterized. Recent findings suggest that deflection from the finely-tuned balance between production and degradation of the bioactive lipids in tissues can ultimately drive physiological metabolic pathways towards pathophysiology, such as cancer. A subset of enzymes in the serine hydrolase family is involved in the regulation of the life cycle of endocannabinoids in the body. Our research team focuses in particular to study and inhibit the function of these lipase enzymes and their role in the mechanisms of migraine and pain conditions.

Research Goals

By combining the expertise represented by our collaborators in the fields of synthetic chemistry and metabolomics, we aim at deeper molecular level understanding on the key players orchestrating lipid signaling in health and disease. Our current efforts focus specifically on the mechanisms of migraine and other pain conditions.

Scientific and Societal Impact of Research

Metabolic enzymes such as lipases and peptidases have a pivotal role in regulating the function of cells in the body. The main focus of our study is to characterize the role of endocannabinoid-degrading enzymes in the development of migraine. By increasing the number of endocannabinoids in tissues and simultaneously, reducing the formation of the degradation products, we can enhance the therapeutic effect of endocannabinoids and prevent the formation of arachidonic acid derivatives (prostaglandins), which particularly increase inflammatory responses. We are also working to develop new selective inhibitors that target these important enzymes and thus, create new alternative therapies for migraine-related headache, one of the most common pain-type worldwide.

Funding
Migraine Research Foundation, https://migraineresearchfoundation.org/