Gistelinck Marc, Lambert Jean-Charles, Callaerts Patrick, Dermaut Bart, Dourlen Pierre
Laboratory of Behavioral and Developmental Genetics, Center for Human Genetics, University of Leuven, 3000 Leuven, Belgium.
Int J Alzheimers Dis. 2012;2012:970980. doi: 10.1155/2012/970980. Epub 2012 Jun 4.
Aggregates of the microtubule-associated protein Tau are neuropathological hallmark lesions in Alzheimer's disease (AD) and related primary tauopathies. In addition, Tau is genetically implicated in a number of human neurodegenerative disorders including frontotemporal dementia (FTD) and Parkinson's disease (PD). The exact mechanism by which Tau exerts its neurotoxicity is incompletely understood. Here, we give an overview of how studies using the genetic model organism Drosophila over the past decade have contributed to the molecular understanding of Tau neurotoxicity. We compare the different available readouts for Tau neurotoxicity in flies and review the molecular pathways in which Tau has been implicated. Finally, we emphasize that the integration of genome-wide approaches in human or mice with high-throughput genetic validation in Drosophila is a fruitful approach.
微管相关蛋白Tau的聚集体是阿尔茨海默病（AD）及相关原发性tau蛋白病的神经病理学标志性病变。此外，Tau在包括额颞叶痴呆（FTD）和帕金森病（PD）在内的多种人类神经退行性疾病中具有遗传学关联。Tau发挥神经毒性的确切机制尚未完全明确。在此，我们概述了过去十年使用遗传模式生物果蝇开展的研究如何促进了对Tau神经毒性的分子理解。我们比较了果蝇中Tau神经毒性的不同可用检测指标，并综述了与Tau相关的分子途径。最后，我们强调将人类或小鼠的全基因组方法与果蝇中的高通量基因验证相结合是一种富有成效的方法。
