Götz Jürgen, Ittner Lars M
Alzheimer's & Parkinson's Disease Laboratory, Brain & Mind Research Institute, University of Sydney, 100 Mallett Street, Camperdown, NSW 2050, Australia.
Nat Rev Neurosci. 2008 Jul;9(7):532-44. doi: 10.1038/nrn2420.
Insoluble protein aggregates have been linked to Alzheimer's disease (AD) and frontotemporal dementia (FTD). Recent work in transgenic mice has shed light on the role of these aggregates by identifying soluble oligomeric species that may interfere with essential cellular mechanisms at an early disease stage. This review summarizes what we have learned about the roles of these proteins from transgenic mice and invertebrate species such as flies and worms. Proteomic and transcriptomic analyses of tissue from these animal models have identified new molecules with crucial roles in disease. Moreover, transgenic animals have been instrumental in defining drug targets and designing novel therapeutic strategies. With advanced imaging techniques that can be used in both humans and mice an early, preclinical diagnosis of AD and FTD could be within reach.
不溶性蛋白质聚集体与阿尔茨海默病(AD)和额颞叶痴呆(FTD)有关。最近在转基因小鼠上的研究通过鉴定可溶性寡聚体物种,揭示了这些聚集体在疾病早期阶段可能干扰基本细胞机制的作用。本综述总结了我们从转基因小鼠以及果蝇和线虫等无脊椎动物物种中了解到的这些蛋白质的作用。对这些动物模型组织的蛋白质组学和转录组学分析已经鉴定出在疾病中起关键作用的新分子。此外,转基因动物在确定药物靶点和设计新的治疗策略方面发挥了重要作用。借助可用于人类和小鼠的先进成像技术,AD和FTD的早期临床前诊断有望实现。