Zebrafish as an Emerging Model for Bioassay-Guided Natural Product Drug Discovery for Neurological Disorders

Abstract

Most neurodegenerative diseases are currently incurable, with large social and economic impacts. Recently, there has been renewed interest in investigating natural products in the modern drug discovery paradigm as novel, bioactive small molecules. Moreover, the discovery of potential therapies for neurological disorders is challenging and involves developing optimized animal models for drug screening. In contemporary biomedicine, the growing need to develop experimental models to obtain a detailed understanding of malady conditions and to portray pioneering treatments has resulted in the application of zebrafish to close the gap between in vitro and in vivo assays. Zebrafish in pharmacogenetics and neuropharmacology are rapidly becoming a widely used organism. Brain function, dysfunction, genetic, and pharmacological modulation considerations are enhanced by both larval and adult zebrafish. Bioassay-guided identification of natural products using zebrafish presents as an attractive strategy for generating new lead compounds. Here, we see evidence that the zebrafish’s central nervous system is suitable for modeling human neurological disease and we review and evaluate natural product research using zebrafish as a vertebrate model platform to systematically identify bioactive natural products. Finally, we review recently developed zebrafish models of neurological disorders that have the potential to be applied in this field of research.

Crosstalk between Different DNA Repair Pathways Contributes to Neurodegenerative Diseases

“…The nematode Caenorhabditis elegans ( C. elegans ) is an example of an animal where its transparent body allows the monitoring of neurodegeneration in vivo. Humanized animal models are available in which transgenic animals express human α-SYN [ 187 , 188 ], Aβ 1–42 , TAU [ 189 , 190 ], TDP-43 and SOD1 [ 191 , 192 , 193 ]. The existence of behavioral assays makes it possible to study viability and functionality from individual neurons during a natural life course.…”

Spatiotemporal analysis of mycolactone distribution in vivo reveals partial diffusion in the central nervous system

“…Originally introduced as a model organism in developmental biology, the zebrafish (Danio rerio) has emerged in recent years as a powerful vertebrate model to study host-pathogen interactions, human diseases, drug screening and toxicology due to its >70% genetic homology with humans and remarkable conservation of biological pathways, major organs and tissues [15][16][17][18]. ML-producing bacteria cause BU-like disease in infected fish [19] and cytotoxicity in cultured fish macrophages [20], suggesting that fish Sec61 is susceptible to inhibition by ML.…”

Erythroxylum pungens Tropane Alkaloids: GC-MS Analysis and the Bioactive Potential of 3-(2-methylbutyryloxy)tropan-6,7-diol in Zebrafish (Danio rerio)

“…The search for biologically active compounds from biological screenings has been successfully applied in the discovery of several types of drugs [6]. In this context, zebrafish (Danio rerio Hamilton, 1822) has been established as an integrative experimental model that closes the gap between in vitro and in vivo testing [7]. Zebrafish has also attracted scientific attention in recent years due to the relatively high genetic similarity with humans (70 % homologous genes), small size, high fecundity, and short developmental cycle, all of which are practical advantages of this vertebrate as a model [8].…”