Endocannabinoid Transport

Research team
Gertsch Jürg PI
Kukulski Wanda Co-PI
Altmann Karl-Heinz Co-PI
Reynoso Ines Postdoctoral Fellow

Endocannabinoids are important physiological lipid modulators of major neurotransmitters in the CNS as well as of immune and metabolic processes. Although there is a lot of knowledge on how endocannabinoids are generated and inactivated, the molecular machinery of endocannabinoid memrbae trafficking is still poorly understood (see the recent review: Nicolussi & Gertsch, 2015). In this project we generate novel molecular tools to study endocannabinoid membrane transport in neurons and immune cells (Reynoso-Moreno et al., 2018, Chicca et al., 2017, Chicca et al., 2012, Nicolussi et al., 2014). We develop selective endocannabinoid reuptake inhibitors as potential therapeutic agents for neuropsychiatric and inflammatory diseases in collaboration with industry partners and the startup company Synendos Therapeutics. We work on new membrane-associated proteins involved in endocannabinoid membrane transport as novel target to modulate the endocannabinoid system.

Relevant literature

Reynoso-Moreno I, Chicca A, Flores-Soto ME, Viveros-Paredes JM, Gertsch J. (2018), The Endocannabinoid Reuptake Inhibitor WOBE437 Is Orally Bioavailable and Exerts Indirect Polypharmacological Effects via Different Endocannabinoid Receptors. Front Mol Neurosci. 28;11:180.

Chicca A, Nicolussi S, Bartholomäus R, Blunder M, Aparisi Rey A, Petrucci V, Reynoso-Moreno IDC, Viveros-Paredes JM, Dalghi Gens M, Lutz B, Schiöth HB, Soeberdt M, Abels C, Charles RP, Altmann KH, Gertsch J. (2017), Chemical probes to potently and selectively inhibit endocannabinoid cellular reuptake. Proc Natl Acad Sci USA. 114(25):E5006-E5015.

Nicolussi S, Gertsch J. (2015) Endocannabinoid transport revisited. Vitam Horm. 98, 441-85.

Chicca A, Marazzi J, Nicolussi S, Gertsch J. (2012) Evidence for bidirectional endocannabinoid transport across cell membranes. J Biol Chem. 287, 34660-82.

Nicolussi S, Chicca A, Rau M, Rihs S, Soeberdt M, Abels C, Gertsch J. (2014) Correlating FAAH and anandamide cellular uptake inhibition using N-alkylcarbamate inhibitors: from ultrapotent to hyperpotent. Biochem Pharmacol. 92, 669-89.