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Screening Of Anti-AD TCM Based On Heat Shock Protein HSP70 Promoter

Posted on:2018-07-07Degree:MasterType:Thesis
Country:ChinaCandidate:Y J WangFull Text:PDF
GTID:2404330533457746Subject:biology
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AD is a chronic neurodegenerative disease whose pathologic features include senile plaques,neurofibrillary tangles,and neuronal loss.Senile plaques are mainly caused by A?,and neurofibrillary tangles are mainly caused by hyperphosphorylation of Tau,which involve the problem of protein misfolding and aggregation.A large number of studies have shown that the etiology of AD is closely related to neuronal dysfunction due to the misfolding protein accumulating in the brain and the resulting neuronal apoptosis.The current treatment of AD is mainly focused on the pathological characteristics of AD itself,there is little drug for the reduction of protein misfolding to prevent and treat AD.Heat shock proteins are able to prevent false folding and aggregation of proteins,re-fold the misfolded protein,especially the heat shock protein HSP70.Studies have shown that HSP70 plays a very important role in reducing aggregation and accumulation of A?,restoring Tau protein in vivo balance,reducing oxidative stress,inhibiting nerve inflammation,so HSP70 can be used as an anti-AD target to screen anti-AD drugs.In this study,HSP70 promoter,EGFP and firefly luciferase have been used as the target gene,the qualitative and quantitative reporter gene,respectively.pHSP70-EGFP and pGL3-HSP70 recombinant vectors were successfully constructed and then transfected into HEK 293 T cells.Thus the screening cell models were successfully constructed.We preferentially screened 35 single herbs which appear more times by collection and statistics of the Chinese ancient prescriptions and proved recipes about senile dementia.We have screened four HSP70 promoter activators,which are Scutellaria baicalensis,Acorus tatarinowii,Valeriana jatamansi jones,Schisandra chinensis.The anti-AD effect of these four Single herb decoction is evaluated by the AD cell model induced by A?25-35,The results show that the four Single herb decoction could reduce the cytotoxicity of A?25-35,and the effect of Scutellaria baicalensis is the best.In addition,scutellaria decoction can inhibit the apoptosis of PC12 cells.So the scutellaria decoction has the potential as an anti-AD drug candidate.
Keywords/Search Tags:Alzheimer's Disease, HSP70, A?25-35, promoter, Single herb
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