报告题目：Discovery of new inhibitors of neuroinflammation by a twisting road starting from a negative control
报告人：Hervé Galons 教授
报告人简介：Hervé Galons，博士，法国国家药学科学院院士，法国巴黎第五大学教授。主要研究领域为激酶抑制剂的合成、作用机制研究以及作为药物进行开发的可能，激酶抑制剂是当前药学研究的一大热点，已发表160余篇研究论文，任国际著名药物期刊《欧洲药物化学杂志》（Eur J Med Chem）的主编。
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.