Role of Calcineurin in Striatal Neurotransmission and its Interaction with Dopamine

Grant Type
Grant Year
Institution Location
Institution Organization Name
Mount Sinai Medical Center
Investigators Name
Chung, Eunyong, PhD

The therapeutic effectiveness of haloperidol and pimozide in Tourette Syndrome suggests that dopaminergic mechanisms may be important in the pathogenesis of this disorder. It is well known that protein phosphyorylation-dephosphorylation is an important signal transduction mechanism for mediating the actions of various neurotransmitters including dopamine. Calcineurin is an enzyme which dephosphorylates several phosphoproteins as well as non-protein phosphoeser in a calcium and calmodulin-dependent manner. Calcineurin is a major calmodulin binding protein in the brain and has been shown to be present in the highest concentration in the striatum. Our studies indicate that calcineurin is primarily located in neurons postsynaptic to nigral dopaminergic input, i.e., neurons containing haloperidol binding sites. Because of its localization and biochemical actions, calcineurin may be a part of regulatory mechanism for dopaminergic neurotransmission. Therefore we propose to investigate whether dephosphorylation via calcineurin is involved in the expression of increased dopaminergic receptor sensitivity following chronic haloperidol treatment. Eunyong Chung, Ph.D. Mount Sinai Medical Center, New York, NY Award: $5,000 Tourette Association of America Inc. – Research Grant Award 1987