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Zebrafish-Based Drug Discovery

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A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: closed (31 August 2023) | Viewed by 16121

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Prof. Dr. Yasuhito Shimada

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Department of Integrative Pharmacology, Mie University Graduate School of Medicine, Tsu, Mie, Japan
Interests: zebrafish; pharmacology; obesity; cancer; natural product; chemical screening
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Special Issue Information

Dear Colleagues,

Zebrafish (Danio rerio) is contributing to speeding up drug discovery in a range of areas, including phenotype-based screening using disease models (so-called “zebrafish screening”), target molecule discovery, validation of the results of cell studies before clinical trials, and toxicological evaluation. As a result, many drug candidates, first-in-class drugs, and several drugs for off-label use have been discovered using zebrafish over the past 10 years. This Special Issue provides a forum to discuss zebrafish-based drug discovery from broader perspectives, including the creation of human disease models, technologies harnessing these as model organisms, and their use for drug or drug candidate identification. Review articles by experts in the field are particularly welcome.

Prof. Dr. Yasuhito Shimada
Guest Editor

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Keywords

drug screening
disease model
obesity
cancer
musculoskeletal diseases
toxicology
neurological disorders

Published Papers (5 papers)

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Research

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22 pages, 3483 KiB

Open AccessArticle

Induction of Liver Size Reduction in Zebrafish Larvae by the Emerging Synthetic Cannabinoid 4F-MDMB-BINACA and Its Impact on Drug Metabolism

by Yu Mi Park, Charlotte Dahlem, Markus R. Meyer, Alexandra K. Kiemer, Rolf Müller and Jennifer Herrmann

Molecules 2022, 27(4), 1290; https://doi.org/10.3390/molecules27041290 - 15 Feb 2022

Cited by 5 | Viewed by 3540

Abstract

Zebrafish (ZF; Danio rerio) larvae have become a popular in vivo model in drug metabolism studies. Here, we investigated the metabolism of methyl 2-[1-(4-fluorobutyl)-1H-indazole-3-carboxamido]-3,3-dimethylbutanoate (4F-MDMB-BINACA) in ZF larvae after direct administration of the cannabinoid via microinjection, and we visualized the spatial distributions of the parent compound and its metabolites by mass spectrometry imaging (MSI). Furthermore, using genetically modified ZF larvae, the role of cannabinoid receptor type 1 (CB1) and type 2 (CB2) on drug metabolism was studied. Receptor-deficient ZF mutant larvae were created using morpholino oligonucleotides (MOs), and CB2-deficiency had a critical impact on liver development of ZF larva, leading to a significant reduction of liver size. A similar phenotype was observed when treating wild-type ZF larvae with 4F-MDMB-BINACA. Thus, we reasoned that the cannabinoid-induced impaired liver development might also influence its metabolic function. Studying the metabolism of two synthetic cannabinoids, 4F-MDMB-BINACA and methyl 2-(1-(5-fluoropentyl)-1H-pyrrolo[2,3-b]pyridine-3-carboxamido)-3,3-dimethylbutanoate (7′N-5F-ADB), revealed important insights into the in vivo metabolism of these compounds and the role of cannabinoid receptor binding. Full article

(This article belongs to the Special Issue Zebrafish-Based Drug Discovery)

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15 pages, 2179 KiB

Open AccessReview

Zebrafish Models for Skeletal Muscle Senescence: Lessons from Cell Cultures and Rodent Models

by Shogo Ichii, Izumi Matsuoka, Fumiyoshi Okazaki and Yasuhito Shimada

Molecules 2022, 27(23), 8625; https://doi.org/10.3390/molecules27238625 - 06 Dec 2022

Cited by 2 | Viewed by 3073

Abstract

Human life expectancy has markedly increased over the past hundred years. Consequently, the percentage of elderly people is increasing. Aging and sarcopenic changes in skeletal muscles not only reduce locomotor activities in elderly people but also increase the chance of trauma, such as bone fractures, and the incidence of other diseases, such as metabolic syndrome, due to reduced physical activity. Exercise therapy is currently the only treatment and prevention approach for skeletal muscle aging. In this review, we aimed to summarize the strategies for modeling skeletal muscle senescence in cell cultures and rodents and provide future perspectives based on zebrafish models. In cell cultures, in addition to myoblast proliferation and myotube differentiation, senescence induction into differentiated myotubes is also promising. In rodents, several models have been reported that reflect the skeletal muscle aging phenotype or parts of it, including the accelerated aging models. Although there are fewer models of skeletal muscle aging in zebrafish than in mice, various models have been reported in recent years with the development of CRISPR/Cas9 technology, and further advancements in the field using zebrafish models are expected in the future. Full article

(This article belongs to the Special Issue Zebrafish-Based Drug Discovery)

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21 pages, 642 KiB

Open AccessReview

Zebrafish: A Pharmacological Model for Learning and Memory Research

by Jen Kit Tan, Faris Hazwan Nazar, Suzana Makpol and Seong Lin Teoh

Molecules 2022, 27(21), 7374; https://doi.org/10.3390/molecules27217374 - 30 Oct 2022

Cited by 4 | Viewed by 3625

Abstract

Learning and memory are essential to organism survival and are conserved across various species, especially vertebrates. Cognitive studies involving learning and memory require using appropriate model organisms to translate relevant findings to humans. Zebrafish are becoming increasingly popular as one of the animal models for neurodegenerative diseases due to their low maintenance cost, prolific nature and amenability to genetic manipulation. More importantly, zebrafish exhibit a repertoire of neurobehaviors comparable to humans. In this review, we discuss the forms of learning and memory abilities in zebrafish and the tests used to evaluate the neurobehaviors in this species. In addition, the pharmacological studies that used zebrafish as models to screen for the effects of neuroprotective and neurotoxic compounds on cognitive performance will be summarized here. Lastly, we discuss the challenges and perspectives in establishing zebrafish as a robust model for cognitive research involving learning and memory. Zebrafish are becoming an indispensable model in learning and memory research for screening neuroprotective agents against cognitive impairment. Full article

(This article belongs to the Special Issue Zebrafish-Based Drug Discovery)

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26 pages, 2047 KiB

Open AccessReview

The Development and Application of Opto-Chemical Tools in the Zebrafish

by Zhiping Feng, Bertrand Ducos, Pierluigi Scerbo, Isabelle Aujard, Ludovic Jullien and David Bensimon

Molecules 2022, 27(19), 6231; https://doi.org/10.3390/molecules27196231 - 22 Sep 2022

Cited by 3 | Viewed by 2274

Abstract

The zebrafish is one of the most widely adopted animal models in both basic and translational research. This popularity of the zebrafish results from several advantages such as a high degree of similarity to the human genome, the ease of genetic and chemical perturbations, external fertilization with high fecundity, transparent and fast-developing embryos, and relatively low cost-effective maintenance. In particular, body translucency is a unique feature of zebrafish that is not adequately obtained with other vertebrate organisms. The animal’s distinctive optical clarity and small size therefore make it a successful model for optical modulation and observation. Furthermore, the convenience of microinjection and high embryonic permeability readily allow for efficient delivery of large and small molecules into live animals. Finally, the numerous number of siblings obtained from a single pair of animals offers large replicates and improved statistical analysis of the results. In this review, we describe the development of opto-chemical tools based on various strategies that control biological activities with unprecedented spatiotemporal resolution. We also discuss the reported applications of these tools in zebrafish and highlight the current challenges and future possibilities of opto-chemical approaches, particularly at the single cell level. Full article

(This article belongs to the Special Issue Zebrafish-Based Drug Discovery)

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15 pages, 1569 KiB

Open AccessReview

Zebrafish—An Optimal Model in Experimental Oncology

by Iwona Kwiatkowska, Justyna Magdalena Hermanowicz, Zaneta Iwinska, Krystyna Kowalczuk, Jolanta Iwanowska and Dariusz Pawlak

Molecules 2022, 27(13), 4223; https://doi.org/10.3390/molecules27134223 - 30 Jun 2022

Cited by 6 | Viewed by 2496

Abstract

A thorough understanding of cancer pathogenesis is a necessary step in the development of more effective and safer therapy. However, due to the complexity of the process and intricate interactions, studying tumor development is an extremely difficult and challenging task. In bringing this issue closer, different scientific models with various advancement levels are helpful. Cell cultures is a system that is too simple and does not allow for multidirectional research. On the other hand, rodent models, although commonly used, are burdened with several limitations. For this reason, new model organisms that will allow for the studying of carcinogenesis stages and factors reliably involved in them are urgently sought after. Danio rerio, an inconspicuous fish endowed with unique features, is gaining in importance in the world of scientific research. Including it in oncological research brings solutions to many challenges afflicting modern medicine. This article aims to illustrate the usefulness of Danio rerio as a model organism which turns out to be a powerful and unique tool for studying the stages of carcinogenesis and solving the hitherto incomprehensible processes that lead to the development of the disease. Full article

(This article belongs to the Special Issue Zebrafish-Based Drug Discovery)

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