Department of Clinical Laboratory, The First Affliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, China.
Clinical Research Center, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, China.
J Alzheimers Dis. 2019;69(2):339-353. doi: 10.3233/JAD-180917.
Tauopathies are a specific type of slow and progressive neurodegeneration, which involves intracellular deposition of fibrillar material composed of abnormal hyperphosphorylation of the microtubule associated protein (MAP) tau. Despite many years of intensive research, our understanding of the molecular events that lead to neurodegeneration is far from complete. No effective therapeutic treatments have been defined, and questions surround the validity and utility of existing animal models. It is an urgent need to develop a novel animal model to study the underlying neurodegenerative mechanisms of tauopathies. Zebrafish models of tauopathies could complement existing models by providing an in vivo platform for genetic and chemical screens in order to identify new therapeutic targets and compounds, meanwhile zebrafish models have permitted discovery of unique characteristics of these genes that could have been difficultly observed in other models. Novel transgenic zebrafish models expressing wild-type or mutant forms of human 4R-tau in neurons have recently been reported. These studies show disease-relevant changes including tau hyperphosphorylation, aggregation and somato-dendritic relocalization. This review highlights the availability of transgenic tau zebrafish models that allow more detailed biochemical studies of tau in the zebrafish CNS to characterize solubility, fibril morphology and further clarify phosphorylation proceedings. Furthermore, a deeper knowledge of the zebrafish brain and a better characterization of tau caused by alterations in neurodegenerative disorders are needed.
tau 病是一种特定类型的缓慢进行性神经退行性疾病，涉及由微管相关蛋白 (MAP) tau 的异常过度磷酸化组成的纤维状物质的细胞内沉积。尽管经过多年的深入研究，我们对导致神经退行性变的分子事件的理解还远远不够。尚未确定有效的治疗方法，现有的动物模型的有效性和实用性也存在疑问。因此，迫切需要开发一种新的动物模型来研究 tau 病的潜在神经退行性机制。tau 病的斑马鱼模型可以通过提供遗传和化学筛选的体内平台来补充现有的模型，以确定新的治疗靶点和化合物，同时斑马鱼模型还允许发现这些基因的独特特征，这些特征在其他模型中可能难以观察到。最近报道了表达神经元中野生型或突变型人 4R-tau 的新型转基因斑马鱼模型。这些研究显示了与疾病相关的变化，包括 tau 过度磷酸化、聚集和体树突再定位。这篇综述强调了可用的转基因 tau 斑马鱼模型，这些模型允许在斑马鱼中枢神经系统中对 tau 进行更详细的生化研究，以表征其溶解度、纤维形态，并进一步阐明磷酸化过程。此外，还需要更深入地了解斑马鱼的大脑，并更好地描述由神经退行性疾病引起的 tau 变化。
