Calcineurin as a possible new target for treatment of Parkinson's disease

It is hypothesized that the immunosuppressive agents cyclosporin A and FK-506 may elicit a dopamine-like effect upon dopaminoceptive neurons in the striatum. When complexed to their immunophilins, these molecules will inhibit calcineurin activity leading to increased phosphorylation of dopamine- and cAMP-regulated phosphoprotein (DARPP-32) and hence, inhibition of protein phosphatase-1 activity. As a net result, intracellular protein phosphorylation increases. One or more of these proteins may, in their phosphorylated form, inhibit the depolarization of the neurons, resulting in a dopamine-like effect.