Neuroprotective Effect of Genistein Against beta Amyloid-Induced Neurotoxicity

ABSTRACT

BACKGROUND: Estrogen is beneficial to patients with Alzheimer's disease but has a limited clinical use due to its proliferative and oncogenic effects on non-neuronal estrogen responsive cells. METHODS: In an attempt to find an estrogen substitute that retains the beneficial effects of estrogen with minimal side effects, we compared the neuroprotective and proliferative effects of genistein, a selective estrogen receptor betaagonist, with those of estrogen. RESULTS: Genistein and 17beta-estradiol showed comparable levels of protection against Abeta-induced death of cultured SH-SY5Y human neuroblastoma cells, which was blocked by an estrogen receptor antagonist, ICI 182, 780. On the other hand, 17beta-estradiol, but not geninstein, induced proliferation of uterine endometrial cells. CONCLUSIONS: Our results suggest genistein as a potential alternative to estrogen in the treatment of Alzheimer's disease.