Mechanisms of calcineurin inhibitor-induced neurotoxicity

Abstract

The calcineurin inhibitors cyclosporin A (CyA) and FK506 are widely used as immunosuppressants in human organ transplantation. The main mechanism for their action is the suppression in T cells of calcineurin activity, a Ca2+ and calmodulin-dependent protein phosphatase. A range of side effects are observed in patients on CyA and FK506, and prominent among them is neurotoxicity. In nerve cells, calcineurin is a critical regulator of a diverse array of proteins, leading to both short- and long-term effects on neuronal excitability and function. Some of these roles include the regulation of synaptic transmission, ion channels, and gene transcription, all of which are important in basic brain fu..