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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License
Article
Development of a Zebrafish Model for Rapid Drug Screening against Alzheimer’s Disease
Author(s)
Wenhai Huang, Chuansheng Li, Zhengrong Shen, Xiaoyu Zhu, Bo Xia and Chunqi Li
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DOI:10.17265/2328-2150/2016.04.004
Affiliation(s)
ABSTRACT
Alzheimer’s disease, the leading cause of dementia in the elderly, is a complex neurodegenerative disorder which leads to a progressive decline in cognitive functions. A rapid screening model is highly demanded for identification and evaluation of novel anti-Alzheimer’s disease drugs from a large numbers of compounds. Until now, numerous studies utilized zebrafish model for drug discovery. Since aluminum can induce a similar biological activity in zebrafish as in Alzheimer patients, in this study, we developed a novel animal model using 3 to 5 day post-fertilization larval zebrafish by optimizing the doses and duration of aluminum chloride exposure. Six anti-Alzheimer’s disease drugs with a variety of mechanisms were tested to validate the newly developed zebrafish model. Importantly, Rivastigmine, ThT, Flurbiprofen and AM-117 could increase the value of Dyskinesia Recovery Rate by 53.4-64%, 169.4-200%, 54.5-96% and 70.9-121%, respectively. Rivastigmine, Memantine, ThT, Flurbiprofen, Rosiglitazone and AM-117 improved the value of Response Efficiency by 86.6-175.1%, 28.2-66.6%, 127.2-236.5%, 118.3-323.7%, 26.6-140.8% and 70.2-161.4%, respectively. Our results suggest that the zebrafish model developed in this study could be a useful tool for high throughput screening of potential novel anti-Alzheimer’s disease leading compounds targeting acetylcholinesterase, N-methyl-D-aspartic acid receptor, γ-secretase, peroxisome proliferator-activated receptor-γ and amyloid-β.
KEYWORDS
Alzheimer’s disease, 3-5dpf Larvae, screening platform, zebrafish model.
Cite this paper
Huang, W., et al. 2016. “Development of a Zebrafish Model for Rapid Drug Screening against Alzheimer’s Disease.” Journal of Pharmacy and Pharmacology 4 (4): 162-173.
References