咪唑对转基因果蝇阿尔茨海默病模型的治疗作用

Effect of Imidazole on Transgene Alzheimer’s Disease of Drosophila Model

目的:研究咪唑对于阿尔茨海默病(AD)果蝇模型学习记忆能力的影响,及其对c-Jun N-Terminal kinas(JNK)的调控。方法:采用Gal4/UAS系统建立Aβ42果蝇模型;连续给药后利用巴甫洛夫嗅觉学习实验观察咪唑对AD果蝇行为的影响;免疫印迹实验检测咪唑干预JNK信号通路中JNK蛋白的磷酸化水平。结果:1 mmol.L-1,100μmol.L-1,10μmol.L-1,1μmol.L-1,0.1μmol.L-1的咪唑可显著改善Aβ42果蝇的学习能力,同时1 mmol.L-1、100μmol.L-1和10μmol.L-1的咪唑显著降低JNK蛋白的磷酸化水平,两者的有效工作浓度近似。结论:咪唑显著改善了Aβ42引起的AD果蝇学习缺陷,且对JNK神经元凋亡信号通路也有明显的调控作用;同时说明Aβ与细胞膜作用形成的通道侧的H13-H14组氨酸侧基,是探索Aβ毒性作用机制和寻找药物治疗的新靶点。

Aim： To observe the effect of imidazole on the learning and memory ofAlzheiemer＇ s disease （AD） drosophila model and the regulation of JNK pathway. Methods： With an extensively characterized Pavlovian olfactory aversive conditioning, the effect of feeding imidazole in Aβ42-expressing flies operated by Ga14/UAS system was probed. The phosphorylation level for JNK pathway were determined by using the Western blot assay. Results： Imidazole can significantly rescue the learning and memory loss induced by Aβ42, and regulate the level of phosphorylation in JNK pathway. There was the similar work concentration. Conclusion： Our data suggested that imidazole may block the Aβ channel by binding to side chains of Aβ residues His 13 and His 14 which have become the new target for therapy.