GPR6

GPR6 is an orphan G protein-coupled receptor that has been associated with the cannabinoid family because of its recognition of a sub-set of cannabinoid ligands. GPR6 is highly expressed in human striatum and hypothalamus. GPR6 has been suggested as a possible target for the treatment of several neurodegenerative diseases. Experimental evidence shows that depletion of GPR6 causes both dopamine increase and cAMP decrease in the striatal tissues which are accompanied by improved movement. Knockout of GPR6 in a Parkinson’s disease mice model results in a decrease of the involuntary movements that characterize this disease. In fact, several patents claim the use of pyrazine derivatives as GPR6 inverse agonists for treating Parkinson’s disease symptoms and other dyskinesia syndromes. GPR6 is also involved in other neurological disorders such as Huntington’s and Alzheimer’s Disease. Moreover, instrumental learning has been shown to be impaired in GPR6 knockout mice models.