Crowther Damian C, Kinghorn Kerri J, Page Richard, Lomas David A
Department of Medicine, University of Cambridge, Cambridge Institute for Medical Research, Wellcome Trust/MRC Building, Hills Road, Cambridge CB2 2XY, UK.
Curr Opin Pharmacol. 2004 Oct;4(5):513-6. doi: 10.1016/j.coph.2004.07.001.
The dominating role of the mouse in modeling Alzheimer's disease has been challenged this year by Drosophila melanogaster. Transgenic flies expressing toxic beta-amyloid peptides develop neurodegeneration. It is these peptides that accumulate in human disease and are thought to be the initiating factor in Alzheimer's disease. The flies exhibit a clear phenotype from a few days of age, including reduced locomotor function, impaired olfactory memory and shortened lifespan. Therapeutic agents that interfere with the generation of toxic aggregates of beta-amyloid peptides have been shown to rescue the flies. Several groups are now using the power and speed of genetic screens in the fly to accelerate the discovery of novel therapeutic agents.
今年,果蝇对小鼠在阿尔茨海默病建模中的主导地位提出了挑战。表达有毒β-淀粉样肽的转基因果蝇会发生神经退行性变。正是这些肽在人类疾病中积累,并被认为是阿尔茨海默病的起始因素。果蝇从几天大时就表现出明显的表型,包括运动功能减退、嗅觉记忆受损和寿命缩短。已证明,干扰β-淀粉样肽有毒聚集体生成的治疗药物可挽救果蝇。现在有几个研究小组利用果蝇基因筛选的强大功能和速度,加速新型治疗药物的发现。