Study On Selective Estrogen Receptor Modulators(SERMs) For Treating AD

Alzheimer’s disease(AD) seriously affected cognitive and memory impairment. Alzheimer’s disease was the normal and most important brain degenerative diseases, and the incidence of AD was significantly increased year by year, in which the incidence of women was 3 times as the incidence of male. Its pathogenesis remained unknown, there are some explains,such as Aβ theory and neural excitotoxicity theory and so on.There is not any specific method for the treatment for alzheimer’s disease, Recent research for anti-AD drugs, primarily for Aβ and tau protein hyperphosphorylation, but their clinical trials ended in failure.Due to the high incidence of patients with post-menopausal women in men, a significant decrease in estrogen in postmenopausal women could improve memory. Estrogen acted as the receptor agonist in central nervous system and other tissues and organs, such as ovarian and uterine,so when it actived the receptor in central nervous system,it also excited the receptor in other organs,so it may cause side effects. And due to the excitement or antagonistic effects of selective estrogen receptor modulators(SERMs) in different tissues, they would not agitate the receptor in other organs when they agitating the receptor in the central nervous system. thus SERMs gradually instead of estrogen.Based on the above theory, the aim of this study is to investigate selective estrogen drugs nerve cell model, ie SHSY5 Y cell in order to discover novel potential anti-AD drugs.The main contents of this study are as follows:(1) A reliable cell model to estimate anti-AD drugs was well established. Cultur SHSY5 Y cell and damag the cell with serum-free, Aβ, glutamic acid, etc., and then select the best conditions and the protective effects of the drug by the methods of MTT, CCK, LDH and so on.(2) Induce the SHSY5 Y cell differentiation and select the best induction and differentiation conditions with the methods of observing the change of cell morphology and detecting the expression of MAP-2 by western blotting and the cellular immunofluorescence(3) Damage differentiated SHSY5 Y cell with serum-free cell Aβ, glutamate and treatment the cell models by SERMs drugs Raloxifene and estrogen then measure their protection.In summary, both undifferentiated and differentiated cells were used to establish a working model, in the present study, and selected drugs Raloxifene detected cell models have a protective effect. Obvious changes in cell morphology was well characterized in induced differentiation experiments under suitable conditions, but no specific proteins was determined. Further investigation on biomarker is necessary in order to better understanding of cell model for.anti-AD drug selection.