Key Laboratory for Protein Sciences of Ministry of Education, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Proc Natl Acad Sci U S A. 2012 Oct 9;109(41):16743-8. doi: 10.1073/pnas.1208011109. Epub 2012 Sep 27.
Current understanding of amyloid-β (Aβ) metabolism and toxicity provides an extensive list of potential targets for developing drugs for treating Alzheimer's disease. We took two independent approaches, including synaptic-plasticity-based analysis and behavioral screening of synthetic compounds, for identifying single compounds that are capable of rescuing the Aβ-induced memory loss in both transgenic fruit fly and transgenic mouse models. Two clinically available drugs and three synthetic compounds not only showed positive effects in behavioral tests but also antagonized the Aβ oligomers-induced activation of the epidermal growth factor receptor (EGFR). Such surprising converging outcomes from two parallel approaches lead us to conclude that EGFR is a preferred target for treating Aβ-induced memory loss.
目前对淀粉样蛋白-β（Aβ）代谢和毒性的理解为开发治疗阿尔茨海默病的药物提供了广泛的潜在靶点。我们采用了两种独立的方法，包括基于突触可塑性的分析和合成化合物的行为筛选，以鉴定能够挽救转基水果蝇和转基因小鼠模型中 Aβ 诱导的记忆丧失的单一化合物。两种临床可用的药物和三种合成化合物不仅在行为测试中显示出积极的效果，而且还拮抗了 Aβ 寡聚物诱导的表皮生长因子受体（EGFR）的激活。这两种平行方法得出的令人惊讶的趋同结果使我们得出结论，EGFR 是治疗 Aβ 诱导的记忆丧失的首选靶标。
