Mutations in presenilins caused most of the autosomal dominant familial forms of Alzheimers disease by altering ? secretase activity. The ? secretase is a large multiprotein complex including presenilin heterodimers,nicastrin,PEN 2 and additional unidentified components.? secretase cleaves beta amyloid precursor protein,Notch,E cadherin,ErbB 4 receptor tyrosine kinase and other membrane proteins.The development of various ? secretase inhibitors not only provides a tool for investigating the structure, function and mechanism of ? secretase,but also presents a therapeutic strategy to slow progression of Alzheimers disease pathology. Threre are various classes of ? secretase inhibitors: compounds containing a difluoro ketone or a difluoro alcohol group, (hydroxyethy) urea peptidomimetics,compounds possessing a hydroxyethylene dipeptide isostere, short helical peptides, non peptidic inhibitors derived from 4 chloro isocoumarin synthon, compounds containing alanyl moiety.Among these species of ? secretase inhibitors,those which selectively affect Abeta production are especially the most promising drugs to treat Alzheimers disease.

Pro-rich antimicrobial peptides are a group of linear peptides isolated from animals. These peptides have antibacterial activities and play an important role in innate immunity. Pro-rich antimicrobial peptides are devided into two classes:Pro-rich antimicrobial peptides from mammals and Pro-rich antimicrobial peptides from insects and other invertebrates.Members of Pro-rich antimicrobial peptides are all characterised by a high content of proline residues and predominantly active against Gram-negative bacterial species which they kill by a non-lytic mechanism,at variance with the majority of the known antimicrobial peptides. Evidence is accumulating that the Pro-rich peptides enter the cells without membrane lysis and,once in the cytoplasm,bind to,and inhibit the activity of DnaK protein that is essential to bacterial growth,thereby causing responsive bacteria death. This mode of action makes these peptides suitable for drug development efforts. As one of the best characterized Pro-rich peptides,PR-39 plays an important role in a number of biological processes. It has been found that PR-39 can induce the syndecan expression in mesenchymal cells, inhibit the NADPH oxidase activity of neutrophils and block the degradation of 1?B? and HIF-1?. These findings show that PR-39 can provide novel means in the control of inflammation, wound repair, ischemia-reperfusion injury,and angiogenesis for therapeutic purposes.

AIM: To explore the effect of microRNA-146a (miR-146a) on apoptosis of human gastric cancer SGC-7901 cells and the underluing mechanism.METHODS: miR-146a mimic (up-regulated miR-146a expression) and miR-146a inhibitor (down-regulated miR-146a expression) were transfected into the SGC-7901 cells by liposome method.At the same time, miRNA nonsense sequence transfection group as the negative control group (NC group) was set up.RT-qPCR was used to evaluate the levels of miR-146a in the SGC-7901 cells after transfection.The effects of miR-146a on the cell apoptosis and growth were assessed by flow cytometry analysis and CCK-8 assay, respectively.The effect of over-expression or knockdown of miR-146a on transforming growth factor-β-activated kinase 1 (TAK1)/ nuclear factor-kappa B (NF-κB) signaling was evaluated by RT-qPCR and Western blot.RESULTS: miR-146a modulated apoptosis of SGC-7901 cells.Over-expression of miR-146a significantly increased apoptosis, whereas knockdown of miR-146a inhibited the apoptosis of SGC-7901 cells.The expression of TAK1 at mRNA and protein levels was significantly decreased when miR-146a mimic was transfected into the SGC-7901 cells (P<0.05).On the contrast, the expression of TAK1 at mRNA and protein were significantly higher in miR-146a inhibitor transfection group than that in NC group (P<0.05), suggesting that miR-146a negatively regulated TAK1 expression.Moreover, knockdown of TAK1 enhanced the apoptosis of SGC-7901 cells (P<0.01), while over-expression of TAK1 inhibited the apoptosis of SGC-7901 cells(P<0.01).Additionally, both over-expression of miR-146a and knockdown of TAK1 led to a prominent increase in the expression of NF-κB inhibitor protein alpha (IκBα) and a significat decrease in B cell lymphoma-2 (Bcl-2) level in the SGC-7901 cells.CONCLUSION: miR-146a significantly promotes apoptosis of SGC-7901 cells by inhibition of NF-κB pathway via targeting TAK1.