Jmh. Anneser et al., Immunosuppressant FK506 does not exert beneficial effects in symptomatic G93A superoxide dismutase-1 transgenic mice, NEUROREPORT, 12(12), 2001, pp. 2663-2665
The immunosuppressant drug FK506 has been shown to exert neuroprotective ef
fects in various model systems via inhibition of the protein phosphatase ca
lcineurin (CN). The enzyme Cu/ Zn-superoxide dismutase (SOD1), which is mut
ated in a familial form of amyotrophic lateral sclerosis (ALS), is an endog
enous regulator of CN. Altered function of CN may therefore be involved in
the pathogenesis of ALS. We tested FK506 in a transgenic mouse model expres
sing mutated SOD1 for potential beneficial effects. This treatment, initiat
ed after onset of symptoms, did not cause a reduction in the decline of mot
or function nor did it prolong survival. These results argue against a cruc
ial role of CN in the process leading to motoneuronal degeneration in SOD1-
mutated mice. NeuroReport 12:2663-2665 (C) 2001 Lippincott Williams & Wilki
ns.