Laboratory of Neurogenetics and Pathobiology, Department of Biochemistry and Molecular Biology, Farber Institute for Neurosciences, Thomas Jefferson University, 900 Walnut Street, JHN410, Philadelphia, PA, 19107, USA.
Brain Struct Funct. 2010 Mar;214(2-3):245-62. doi: 10.1007/s00429-009-0234-4. Epub 2009 Dec 5.
Alzheimer's disease (AD) is the most common form of senile dementia. Aggregation of the amyloid-beta42 peptide (Abeta42) and tau proteins are pathological hallmarks in AD brains. Accumulating evidence suggests that Abeta42 plays a central role in the pathogenesis of AD, and tau acts downstream of Abeta42 as a modulator of the disease progression. Tau pathology is also observed in frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17) and other related diseases, so called tauopathies. Although most cases are sporadic, genes associated with familial AD and FTDP-17 have been identified, which led to the development of transgenic animal models. Drosophila has been a powerful genetic model system used in many fields of biology, and recently emerges as a model for human neurodegenerative diseases. In this review, we will summarize key features of transgenic Drosophila models of AD and tauopathies and a number of insights into disease mechanisms as well as therapeutic implications gained from these models.
阿尔茨海默病（AD）是最常见的老年痴呆症形式。淀粉样蛋白-β42 肽（Abeta42）和 tau 蛋白的聚集是 AD 大脑中的病理标志。越来越多的证据表明，Abeta42 在 AD 的发病机制中起核心作用，而 tau 作为 Abeta42 的下游物质，是疾病进展的调节剂。tau 病理学也存在于与 17 号染色体相关的额颞叶痴呆伴帕金森病（FTDP-17）和其他相关疾病中，因此被称为 tau 病。虽然大多数病例是散发性的，但已确定与家族性 AD 和 FTDP-17 相关的基因，这导致了转基因动物模型的发展。果蝇一直是生物学许多领域中强大的遗传模型系统，最近也成为人类神经退行性疾病的模型。在这篇综述中，我们将总结 AD 和 tau 病的转基因果蝇模型的主要特征，以及从这些模型中获得的对疾病机制和治疗意义的一些见解。
