Genistein is neuroprotective in murine models of familial amyotrophic lateral sclerosis and stroke

Amyotrophic lateral sclerosis (ALS), whether sporadic or familial (FALS), i s a progressive, fatal neurodegenerative disorder involving the motor neuro ns of the cortex, brain stem, and spinal cord. In some studies, the male/fe male ratio of ALS patients was as high as 2 to 1. In FALS mice, disease ons et and mortality were earlier among males than among females. This sexual d imorphism was due to estrogen, as treatment with genistein, a phytoestrogen , eliminated the observed sexual dimorphism in FALS mice. Genistein treatme nt also protected against oxygen singlet-induced cerebral damage in vivo. H owever, sexual dimorphism was not observed in this model of stroke; and gen istein was equally effective in males and females. These data suggest that genistein has both estrogen-dependent and estrogen-independent neuroprotect ive activities and it should be investigated as a prophylactic agent agains t pathologic conditions such as ALS and stroke, (C) 1999 Academic Press.