Selective Estrogen Receptor Modulators On SHSY5Y Neuronal Cell Toxicity Of Protection And Mechanism Research

Alzheimer's disease(AD) is a set of primary degenerative disease of unknown etiology. Found among premenopausal women in recent years the incidence of AD is far lower than the male, age and the incidence of AD in postmenopausal women the crowd for the age of 2 to 3 times. Post-menopausal women with the age biggest difference is that estrogen level serious decline, so researchers suggest is due to a decrease in the level of estrogen in women led to the increased incidence of Alzheimer's disease. Clinical applies the estrogen replacement therapy, found in Alzheimer's disease do have therapeutic effect. Estrogen replacement therapy, however, it need to use for more than 10 years and has stimulation to the endometrium, have led to the risk of breast cancer and endometrial cancer. So now, find the class estrogen effect of drug is imminent.Selective estrogen receptor modulators(SERMs) are similar to estrogen, and in the different target groups have different selective, characterized by the effect of estrogen agonist or antagonist, and estrogen is by influencing the silk crack the original amp-activated protein kinase(MAPK) signaling pathway to regulate cell mitochondrial function to give play to the role of neural protection, so we speculated that selective estrogen receptor modulators(SERMs) and the signal pathways through effect into full play. So this topic is to find a kind of effective for Alzheimer's selective estrogen receptor modulators, and the second generation of selective estrogen receptor modulators(SERMs) representative drugs raloxifene(RLX) role in the protection of the central nervous mixed reviews.This subject mainly research the second generation of selective estrogen receptor modulators(SERMs) raloxifene(RLX) for A? 1-40 induction of human glioma cells(SHSY5Y) protective effect and its mechanism of toxicity.The first part of SERMs protective effect of nerve cellsObjective: to study the second generation of SERMs raloxifene(RLX) effect on A? 1-40 SHSY5 Y cells of protection.Methods: cultivating SHSY5 Y cells by all trans retinoic acid(RA) differentiation, to A?1-40 after processing cause alzheimer's disease model, thedifferent concentrations of 17? estradiol, estradiol benzoate and raloxifene on its protection, and Hoechst33258 dye observation of cell apoptosis.Results:(1) A? process can cause cell vitality decline, increased apoptosis;(2) RLX similar to estrogen, can increase the cell's vigor, A? process has protective effect to the nerve cells, and to reduce its apoptosis.The second part of SERMs mechanism of nerve cellsObjective: to study the second generation of SERMs raloxifene(RLX) for A? role of the mechanism of action of SHSY5 Y cells, verify through MAPK signal pathway to play to the effect of nerve cellsMethods: using ERK1/2 inhibitor PD98059, p38 MAPK inhibitor and JNK inhibitors AD model CEP1347 cells, by determined by MTT, CCK8, JC- 1 staining fluorescence microscope and Western Blot protein detection analysis technology, study of raloxifene in neural protection mechanism.Results: find SHSY5 Y cells induced by p38 MAPK and JNK activation leads to cell mitochondrial pathways of apoptosis, and there are some aspects of synergy. The RLX can activate the ERK signaling pathway to protect A? 1-40 induced SHSY5 Y cells, inhibit p38 MAPK and JNK activation, thus inhibiting mitochondrial pathways of apoptosis cells.