Use of Zebrafish Genetic Models to Study Etiology of the Amyloid-Beta and Neurofibrillary Tangle Pathways in Alzheimer's Disease.
Use of Zebrafish Genetic Models to Study Etiology of the Amyloid-Beta and Neurofibrillary Tangle Pathways in Alzheimer's Disease.
复制标题
DOI：
10.2174/1570159x19666210524155944
复制
发表时间：
2022-03-04
影响因子：
5.3
通讯作者：
中科院分区：
文献类型：
--
作者：
全球神经退行性疾病的流行率正在上升，迫切需要确定和扩大药物治疗策略的可获得性。阿尔茨海默病是最常见的神经退行性疾病，目前尚无治愈方法，治疗方法也有限。啮齿动物模型主要用于阿尔茨海默病的研究，以调查病因、病理学、分子机制和药物治疗。然而，对阿尔茨海默病的病因、发病机制和最佳治疗缺乏全面的了解，部分原因是使用啮齿动物的一些限制，包括较高的经济成本，这可能会影响样本大小和最终的统计能力。有必要扩展我们的动物模型工具箱，为阿尔茨海默病的研究提供替代策略。斑马鱼在神经退行性疾病研究和神经药理学中的应用正在极大地扩大，因为它具有以下几个重要优势：较低的经济成本、较小的有机体大小、具有序列特征的基因组以及描述良好的解剖结构。这些特征与人类保守的分子功能和疾病途径有关。斑马鱼中与阿尔茨海默病相关基因的同源基因的存在也得到了证实。虽然野生斑马鱼似乎缺乏阿尔茨海默病的一些神经病理特征，但基因编辑技术的出现扩大了使用斑马鱼评估淀粉样蛋白和神经原纤维缠结假说的范围，并探索了药物分子靶标。详细介绍了如何在斑马鱼上使用基因编辑技术来创建模型，以研究阿尔茨海默病的原因、病理、分子机制和药物靶点。
The prevalence of neurodegenerative diseases is increasing globally, with an imperative need to identify and expand the availability of pharmaceutical treatment strategies. Alzheimer's disease is the most common neurodegenerative disease for which there is no cure and limited treatments. Rodent models are primarily used in Alzheimer's disease research to investigate causes, pathology, molecular mechanisms, and pharmaceutical therapies. However, there is a lack of a comprehensive understanding of Alzheimer's disease causes, pathogenesis, and optimal treatments due in part to some limitations of using rodents, including higher economic cost, which can influence sample size and ultimately statistical power. It is necessary to expand our animal model toolbox to provide alternative strategies in Alzheimer's disease research. The zebrafish application in neurodegenerative disease research and neuropharmacology is greatly expanding due to several vital strengths spanning lower economic costs, the smaller size of the organism, a sequenced characterized genome, and well described anatomical structures. These characteristics are coupled to the conserved molecular function and disease pathways in humans. The existence of orthologs for genes associated with Alzheimer's disease in zebrafish is also confirmed. While wild-type zebrafish appear to lack some of the neuropathological features of Alzheimer's disease, the advent of genetic editing technologies has expanded the evaluation of the amyloid and neurofibrillary tangle hypotheses using the zebrafish and exploration of pharmaceutical molecular targets. An overview of how genetic editing technologies are being used on the zebrafish to create models to investigate the causes, pathology, molecular mechanisms, and pharmaceutical targets of Alzheimer's disease is detailed.
DOI：
10.1007/978-1-4939-1862-1_17
发表时间：
2015
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Bedell, Victoria M;Ekker, Stephen C
通讯作者：
Ekker, Stephen C