PI3K/AKT Signaling Pathway In Alzheimer's Disease

BackgroundOverproduction and accumulation ofβ-amyloid (AP) have been proposed to be an initiating factor of neuron loss in Alzheimer's disease (AD). AKT is a pivotal molecule in regulating neuronal survival; however, it is still not known whether upregulation of AKT can protect the cells from the Aβ-induced apoptosis.ObjectStudy on the role of upregulation akt against the Aβ-induced apoptosis in the HEK293 cells.MethodsWe divided the cells into five groups.including control group, AP(1-42) group,vector group,AKTwt group,AKTwt+wortmanine group,and treated the HEK293 cells with 20uM AP(1-42) besides control group.By using AnnexinV- PI double-colouring and flow cytometry,cell viability and cell apoptosis was assayed,the AKTmRNA was detected by RT-PCR. Western blot investigates AKT,caspase-3 bad,bax, Bcl-xL, Bcl-w expression and JNK phosphorylation.ResultsIn the present study that upregulation AKT could significantly attenuate the cell apoptosis induced by Aβ(1-42),we also find that the caspase-3,bad,bax expressed in the Aβgroup obviously higher than in the akt group through western blot,moreover the results show that the expression level of Bcl-xL, Bcl-w is significantly decreased in the Aβgroup. Upregulation AKT reduced JNK phosphorylation, and the wortmanine eliminated the effects of overexpressed akt.Conclusionthese results moreoverly suggest that upregulation AKT attenuate Aβinduced apoptosis mainly through reduced JNK phosphorylation,which regulated the gene balance of acceleration and inhibition apoptosis. the signaling of PI3K/AKT could be a promising therapeutic strategy for arresting AP toxicity in AD patients BackgroundAlzheimer's disease is a neurodegenerative disease characterized by the accumulation of beta amyloid into amyloid deposits and by the hyperphosphorylation of the protein tau,leading to neurofibrillary tangles. In addition to tau, abnormally hyperphosphorylated neurofilament is also the protein component of NFTs.β-amyloid peptide could increased the phosphorylation of tau by activating the Gsk-3β. it is still not known whether upregulation of AKT can attenuates the Aβ-induced tau hyperphosphorylation.ObjectStudy the changes and mechanism of upregulation akt on the Aβinduced tau phosphorylation.MethodsAfter transiently transfected AKTwt in the HEK293 cells, which treated with 20uM Aβ(1-42). Western blot detects the phosphorylation sites of S396, S214, S404, tau-1, tau-5 and pSer9-Gsk3βT-Gsk3β, mL309PP2A, dmLeu309PP2A, PTP1B.Resultsthe results shows that:(1) S396,S214,S404 sites obviously decreased in the cells of upregulation AKT. (2) p-GSK3β-Ser9 increased, m-PP2A-Leu309 increased. (3) upregulation AKT increased PTP1B expressionConclusionThese results indicated that upregulation AKT attenuates the Aβinduced tau phosphorylation.which mainly through increased the activity of PP2A through the signaling of PTP1B.