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.
Wera
S
S
Laboratoire de Biologie Molećulaire, Institut de Chime B6, Université de Liége, Sart-Tilman, Belgium.
Neyts
J
J
D019703:Calcineurin; D002148:Calmodulin-Binding Proteins / Q000037:antagonists & inhibitors*; D003342:Corpus Striatum / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism; D010300:Parkinson Disease / Q000628:therapy*; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors*; D010766:Phosphorylation; D054645:Protein Phosphatase 1
D002148:Calmodulin-Binding Proteins; D007166:Immunosuppressive Agents; D019703:Calcineurin; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D004298:Dopamine