G蛋白偶联受体/分泌酶复合体调节阿尔兹海默症发病进程的新机制

Novel regulatory mechanisms of the GPCR/secretase complex on the pathogenesis of Alzheimer′s disease

目的目前对于特异性调控分泌酶剪切淀粉样蛋白前体蛋白的分子机制尚不十分清楚,而临床上抗阿尔兹海默症(A lzhe im ers′D isease,AD)药物的疗效也不足以从根本上缓解病理症状的恶化。对G-蛋白偶联受体(G-prote in coup led receptors,GPCR s)在AD疾病进程的调节机制相关研究进展予以总结,对于以GPCR作为药物靶点的潜在可能性进行讨论。方法对于特异性调控分泌酶剪切淀粉样蛋白前体蛋白的分子机制相关的细胞生物学领域以及AD疾病模型上对于发病机制的研究进展进行总结归纳,并针对该领域的几个重要科学问题进行讨论。结果与结论GPCR对于AD疾病进程的调节机制,尤其是其与分泌酶形成的复合体对于β-淀粉样蛋白(amyloid-,βAβ)产生以及AD发病的调节机制,具有理想的特异性,可成为抗AD药物的新型潜在靶点。

Objective To review the mechanistic studies on G protein-coupled receptors′（GPCRs）regulatory roles in the progress of Alzheimer′s Disease（AD）,and to discuss the potentials of targeting GPCRs to develop novel anti-AD drugs or therapeutic strategies with less side-effects and better clinical efficacy.Methods Cell biology and animal model based recent research progress in the field was reviewed in this article and a few hot topics related to the topic were discussed.Results and Conclusions A list of GPCRs regulate the pathogenesis of AD through a substrate specific mechanism and show great potentials to be utilized as the novel therapeutic targets for AD prevention and treatment.