Study On The Improvement Of New MGluR Antagonist Drugs On Fragile X Syndrome Drosophila Model

Fragile X syndrome(FXS), as one of the most common hereditary mental retardation disease, is caused by the reduce or lack of fragile X mental retardation protein due to the abnormal FMR1gene, accompanied by some discernible clinical symptoms such as autism, mental retardation and irregular sleep, etc. FMRP is a kind of mRNA binding protein, which controls the expression of membrane mRNA translation inhibitory factor negatively regulates postsynaptic. Researchers speculated that the deficiency or decrease of FMRP may lead to excessive interpretation of mRNA stimulated by mGluR. The abnormally active mGluR signal pathway may lead to over-development of nervous system protein, then hinder the development of dendritic spine.Objective:Using the Fragile X drosophila model, disease phenotypes of Fragile X-related symptoms that caused by FMRP deficiency could be simulated, presupposing that the inactivation of dfmrl leads to deficiency in human-like social interaction, learning and memory activity.Methods:With the help of Pharmacy College, several kinds of mGluR antagonist drugs extracted from natural plants were selected to be used in drug screening in FX drosophila model, including JBA, JB1, JB2, JB3, LHP, lgr, and MPEP (2-Methyl-6-phenylethynyl-pyridin). Results:the result shows that JBA can restore the defects on social interaction, immediate response and short-term memory of FX drosophila; JB3can restore the defects on immediate response and short-term memory in FX drosophila; JB1can restore the defects of social interaction and immediate response in FX drosophila; LHP can restore the defects of social interaction in FX drosophila. The results that MPEP drugs can restore the defects of social interaction, immediate response and short-term memory in FX drosophila were confirmed in the experiment.Conclusion:Among them, JBA was identified as the best mGluR antagonist drug in restoring arrhythmic circadian phenotypes in FX drosophila for both Larva and adult drosophila. Through the comparison, researcher could confirm effective molecular structure of MPEP, which lays the theoretical foundation for study on treatment for fragile X syndrome.