[Introduction] Increasing Alzheimer's disease (AD) is a social problem in an aging society. In addition, the prevalence of osteoporosis increases with aging and various interventions are being performed. The hypothesis that aggregates and accumulation of Amyloid beta(Aβ) induces nerve cell death has been proposed. Raloxifene(Ral), a therapeutic agent for postmenopausal osteoporosis, is a selective estrogen receptor modifier, but it is controversial about slowing the progression of AD. Therefore, we investigated the protective effects of Ral on Aβ-induced cytotoxicity.
[Method] The effect of Ral on the aggregation of Aβ was measured by the thioflavin T fluorescence method. In addition, highly toxic Aβ42 oligomer (Aβo) was exposed to human neuroblastoma cells (SH-SY5Y) to induce cytotoxicity. The effects of Ral on Aβo-induced cell damage were assessed by cell viability (MTT), oxidative stress (ROS production, cell membrane phospholipid peroxide) and intracellular Ca²⁺.
[Results] Ral inhibited Aβ42 and Aβ40 aggregation in concentraiton-dependent manner. The effect of Ral on the cytotoxicity of cells induced by Aβo exposure showed an increase in cell viability and a decrease in oxidative stress, and repair of membrane damage. Ral reduced the sustained increase in intracellular Ca²⁺ due to Aβo exposure.
[Conclusion] Ral, a therapeutic agent for osteoporosis, has showed a protective effect against Aβo-induced nerve damage by inhibiting Aβ aggregation and antioxidant effects. Ral is expected to have beneficial effects on the prevention and progression of AD.