Article: article from journal or magazin.
Immunosuppressant FK506 does not exert beneficial effects in symptomatic G93A superoxide dismutase-1 transgenic mice.
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
The immunosuppressant drug FK506 has been shown to exert neuroprotective effects in various model systems via inhibition of the protein phosphatase calcineurin (CN). The enzyme Cu/Zn-superoxide dismutase (SOD1), which is mutated in a familial form of amyotrophic lateral sclerosis (ALS), is an endogenous regulator of CN. Altered function of CN may therefore be involved in the pathogenesis of ALS. We tested FK506 in a transgenic mouse model expressing mutated SOD1 for potential beneficial effects. This treatment, initiated after onset of symptoms, did not cause a reduction in the decline of motor function nor did it prolong survival. These results argue against a crucial role of CN in the process leading to motoneuronal degeneration in SOD1-mutated mice.
Amino Acid Substitution, Amyotrophic Lateral Sclerosis/drug therapy, Amyotrophic Lateral Sclerosis/genetics, Animals, Behavior, Animal/drug effects, Calcineurin/antagonists & inhibitors, Disease Models, Animal, Disease Progression, Dose-Response Relationship, Drug, Humans, Immunosuppressive Agents/administration & dosage, Injections, Intraperitoneal, Mice, Mice, Transgenic, Motor Activity/drug effects, Mutation, Superoxide Dismutase/genetics, Survival Rate, Tacrolimus/administration & dosage, Treatment Failure
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