Dey Shreya, Thamaraikani Tamilanban, Vellapandian Chitra
Pharmacy/Pharmacology, SRM College of Pharmacy, SRM Institute of Science and Technology, Chengalpattu, IND.
Cureus. 2024 Aug 15;16(8):e66935. doi: 10.7759/cureus.66935. eCollection 2024 Aug.
Alzheimer's disease (AD) is a neurological condition that progressively impairs cognitive function and results in memory loss. Despite substantial research efforts, little is known about the specific processes driving AD, and there are few proven therapies. Because of their physiological and genetic resemblance to humans, zebrafish () have become an important model organism for furthering research on AD. This abstract discusses the difficulties faced, looks at the insights currently garnered from zebrafish models, and suggests future research options. AD knowledge has greatly benefited from the use of zebrafish models. Transgenic zebrafish that express human AD-associated genes, such as tau and amyloid precursor protein (APP), display tau neurofibrillary tangles (NFTs) and amyloid-beta (Aβ) plaques, two of the disease's main clinical characteristics. These models have clarified the roles of oxidative stress, inflammation, and calcium homeostasis in the course of AD and allowed for the purpose of high-throughput screening of potential therapeutic agents. Understanding the growth and deterioration of neurons has been greatly aided by real-time zebrafish imaging. Fully using zebrafish models in AD research requires addressing a number of issues. The dissimilarities in zebrafish anatomy and physiology from humans, the difficulty of developing models that replicate progressive and late-onset AD (LOAD), and the requirement for standardized procedures to evaluate alterations in zebrafish cognition and behavior are a few issues. Furthermore, variations in the genetic makeup of zebrafish strains might affect the results of experiments. Future directions include developing standardized behavioral assays and cognitive tests, working together to create extensive databases of zebrafish genetic and phenotypic data, and using genetic engineering techniques like CRISPR/Cas9 to create more complex zebrafish models. Combining zebrafish models with other model species helps expedite the conversion of research results into therapeutic applications and offers a more thorough knowledge of AD. To sum up, zebrafish models have made a substantial contribution to Alzheimer's research by offering insightful information on the causes of the illness and possible therapies. By tackling present issues and formulating a planned future path, we can improve the use of zebrafish to decipher the mysteries of Alzheimer's and help create successful treatments.
阿尔茨海默病(AD)是一种神经疾病,会逐渐损害认知功能并导致记忆丧失。尽管进行了大量研究,但对于驱动AD的具体过程仍知之甚少,且几乎没有经过验证的疗法。由于斑马鱼在生理和基因上与人类相似,它们已成为推动AD研究的重要模式生物。本摘要讨论了面临的困难,审视了目前从斑马鱼模型中获得的见解,并提出了未来的研究方向。斑马鱼模型极大地促进了对AD的了解。表达人类AD相关基因(如tau和淀粉样前体蛋白(APP))的转基因斑马鱼会出现tau神经原纤维缠结(NFTs)和β淀粉样蛋白(Aβ)斑块,这是该疾病的两个主要临床特征。这些模型阐明了氧化应激、炎症和钙稳态在AD病程中的作用,并有助于进行潜在治疗药物的高通量筛选。实时斑马鱼成像极大地辅助了对神经元生长和衰退的理解。要在AD研究中充分利用斑马鱼模型,需要解决一些问题。斑马鱼与人类在解剖学和生理学上的差异、开发能够复制进行性和晚发性AD(LOAD)的模型的困难,以及评估斑马鱼认知和行为变化所需的标准化程序等都是一些问题。此外,斑马鱼品系基因组成的差异可能会影响实验结果。未来的方向包括开发标准化的行为测定和认知测试、共同创建广泛的斑马鱼遗传和表型数据数据库,以及使用CRISPR/Cas9等基因工程技术创建更复杂的斑马鱼模型。将斑马鱼模型与其他模型物种相结合有助于加快研究成果向治疗应用的转化,并提供对AD更全面的认识。总之,斑马鱼模型通过提供有关疾病病因和可能疗法的深刻信息,为阿尔茨海默病研究做出了重大贡献。通过解决当前问题并规划未来的计划路径,我们可以更好地利用斑马鱼来解开阿尔茨海默病的谜团,并帮助开发出成功的治疗方法。