Abstract：
AD disease (AD) is a multifaceted and intricate neurodegenerative disorder characterized by intracellular neurofibrillary tangle (NFT) formation and the excessive production and deposition of Aβ senile plaques. While transgenic AD models have been found instrumental in unravelling AD pathogenesis, they involve cost and time constraints during the preclinical phase. Zebrafish, owing to their simplicity, well-defined behavioural patterns, and relevance to neurodegenerative research, have emerged as a promising complementary model. Zebrafish possess glutaminergic and cholinergic pathways implicated in learning and memory, actively contributing to our understanding of neural transmission processes. This review sheds light on the molecular mechanisms by which various neurotoxic agents, including okadaic acid (OKA), cigarette smoke extract, metals, and transgenic zebrafish models with genetic similarities to AD patients, induce cognitive impairments and neuronal degeneration in mammalian systems. These insights may facilitate the identification of effective neurotoxic agents for replicating AD pathogenesis in the zebrafish brain. In this comprehensive review, the pivotal role of zebrafish models in advancing our comprehension of AD is emphasized. These models hold immense potential for shaping future research directions and clinical interventions, ultimately contributing to the development of novel AD therapies.
摘要：
AD疾病（AD）是一种多方面且复杂的神经退行性疾病，其特征是细胞内神经原纤维缠结（NFT）形成以及Aβ老年斑的过度产生和沉积。虽然已发现转基因AD模型有助于揭示AD发病机理，它们涉及临床前阶段的成本和时间限制.斑马鱼,由于它们的简单性，定义明确的行为模式，以及与神经退行性研究的相关性，已经成为一种有前途的互补模式。斑马鱼拥有与学习和记忆有关的谷氨酸和胆碱能途径，积极促进我们对神经传递过程的理解。这篇综述揭示了各种神经毒性剂的分子机制，包括冈田酸（OKA），香烟烟雾提取物，金属，和转基因斑马鱼模型与AD患者的遗传相似性，在哺乳动物系统中诱导认知障碍和神经元退化。这些见解可能有助于鉴定在斑马鱼大脑中复制AD发病机理的有效神经毒性剂。在这次全面审查中，强调了斑马鱼模型在促进我们对AD的理解中的关键作用。这些模型具有塑造未来研究方向和临床干预的巨大潜力，最终有助于新型AD疗法的开发。
