報(bào)告題目：Discovery of new inhibitors of neuroinflammation by a twisting road starting from a negative control

　　報(bào)告人：Hervé Galons 教授

　　報(bào)告時(shí)間：12月7日（星期四）下午2點(diǎn)

　　報(bào)告地點(diǎn)：生命科學(xué)學(xué)院28-223報(bào)告廳

　　報(bào)告人簡(jiǎn)介：

　　Hervé Galons,，博士,，法國國家藥學(xué)科學(xué)院院士，法國巴黎第五大學(xué)教授,。主要研究領(lǐng)域?yàn)榧っ敢种苿┑暮铣?、作用機(jī)制研究以及作為藥物進(jìn)行開發(fā)的可能，激酶抑制劑是當(dāng)前藥學(xué)研究的一大熱點(diǎn),，已發(fā)表160余篇研究論文,，任國際著名藥物期刊《歐洲藥物化學(xué)雜志》（Eur J Med Chem）的主編。

　　報(bào)告主要內(nèi)容：

　　Neuroinflammation is a critical step in neurodegeneration and consequently contributes to many diseases such as Alzheimer’s disease.

　　The present research started with the design of a negative control.  A negative control is to be used in a large number of experiments. It turns out that this negative control （AFT1） had an off target which was not observed with the positive control （probe）,。

　　The negative control was able to modify the activity of g-secretase leading to an increase of potentially neurotoxic peptides. Structurally analogues of AFT1 were prepared and tested.  Several of these compounds were found to be more potent than AFT1 in the formation of neurotoxic peptides.

　　At this stage, one could wonder whether AFTs could induce cognitive disorders following prolonged administration in animals.

　　Mice were treated with an AFT. The product appeared to be distributed in the brain and, in contrast to the previous hypothesis, was able to rescue cognitive deficits associated with aging.

　　The mechanism of action of this family of compounds has been investigated and will be discussed.