Immunosuppressant FK506 does not exert beneficial effects in symptomatic G93A superoxide dismutase-1 transgenic mice.
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.
Anneser
J M
JM
Department of Neurology, Ludwig-Maximilians-University, Klinikum Grosshadern, D-81366 Munich, Germany.
Gmerek
A
A
Gerkrath
J
J
Borasio
G D
GD
Heumann
R
R
D019943:Amino Acid Substitution; D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy* / Q000235:genetics; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D065095:Calcineurin Inhibitors; D004195:Disease Models, Animal; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007274:Injections, Intraperitoneal; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity / Q000187:drug effects; D009154:Mutation; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1; D015996:Survival Rate; D016559:Tacrolimus / Q000008:administration & dosage*; D017211:Treatment Failure
D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; C000606290:SOD1 protein, human; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D016559:Tacrolimus