Atorvastatin Attenuates Cognitive Deficits By A?1-42 Involving Modulation Of MAPK/ERK And PI3K/AKT Pathway

Purpose:Excessive A?accumulates outside the cells to form neuroinflammatory plaques?NP?and tau protein phosphorylation to form neurofibrillary tangles?NFTs?are the most common pathological mechanism of Alzheimer's disease?AD?.High cholesterol can increase the production of A?and it is an important risk factor for Alzheimer's disease.The cholesterol-lowering drug atorvastatin can reduce cholesterol levels,inhibit the production of A?in the brain,reduce the deposition of neuroinflammatory plaques and tau protein phosphorylation and improve neurological and cognitive function.The purpose of this article is to study the potential molecular mechanism of atorvastatin in reducing the risk of Alzheimer's disease.Experimental Design:First the SH-SY5Y cell were pretreated with atorvastatin for 30 minutes and conducted A?_1-42for 24 hours in 37?incubator.The suitable concentration of atorvastatin was screened by MTT assay.The FDA/PI and Hoechst 33342 staining were applied to analyze cell apoptosis.Novel objective recognition,Y maze and Step down test were tested the cognitive function of bilateral hippocampal injection of A?_1-42in mice after intragastric administration of atorvastatin.The westem blotting analysis was applied to measure protein expression levels involved in proliferation and apoptosis pathways.Results:Atorvastatin pretreatment has a certain protective effect on A?_1-42-induced SH-SY5Y cell death.The results of AD mice experiment show that atorvastatin could improve the cognitive function of AD mice.Western blotting analysis also shows that the expression of anti-apoptotic protein?PAKT/AKT?is up-regulated and apoptotic protein?PERK/ERK?is down-regulated in atorvastatin treated group,which further confirms its neuroprotective effect.Conclusion:Atorvastatin attenuates A?_1-42-induced SH-SY5Y cell death and improves the cognitive function of AD mice through MAPK/ERK and PI3K/AKT pathways.Atorvastatin ameliorates A?_1-42-induced cognitive impairment through MAPK/ERK and PI3K/AKT pathways.