Immunophilin-binding agents prevent glutamate neurotoxicity associated with vascular stroke and neurodegenerative diseases

摘要

Immunophilin-binding agents inhibit the phosphatase calcineurin, leading to the increased phosphorylation of certain brain proteins, including nitric oxide synthase. The increased levels of phosphorylation of nitric oxide synthase inhibits the enzymatic production of nitric oxide. Thus the neurotoxic effects of glutamate, which are ordinarily the result of vascular strokes and other neurodegenerative diseases, are minimized, because the neurotoxic effects are at least partially mediated by nitric oxide. Thus immunophilin-binding drugs can be used therapeutically in the treatment of vascular stroke and neurodegenerative disorders such as Alzheimer's disease and Huntington's disease.