Drug reprofiling using zebrafish identifies novel compounds with potential pro-myelination effects

Buckley, Clare E; Marguerie, Anita; Roach, A. G.; Goldsmith, Paul C.; Fleming, Angeleen; Alderton, Wendy K.; Franklin, Robin J.M.

doi:10.1016/j.neuropharm.2010.04.014

Cited by 73 publications

(52 citation statements)

References 56 publications

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“…Given their suitability for chemical screening and the fact that such screens have lead to clinical trials for other conditions (North et al 2007;Yuelling et al 2012;Cutler et al 2013), zebrafish larvae have been used to identify compounds that promote OL differentiation (Buckley et al 2010). Combining new live reporters of myelin (Almeida et al 2011) and transgenic systems to ablate OLs (Chung et al 2013a), with large-scale chemical screens, will help identify compounds that modify the response to glial damage and the consequent repair process, and thus be of potential therapeutic importance in the future.…”

Section: Oligodendrocytes During Injury and Diseasementioning

confidence: 99%

Glial Cell Development and Function in Zebrafish

Lyons

Talbot

2014

Cold Spring Harb Perspect Biol

125

100

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The zebrafish is a premier vertebrate model system that offers many experimental advantages for in vivo imaging and genetic studies. This review provides an overview of glial cell types in the central and peripheral nervous system of zebrafish. We highlight some recent work that exploited the strengths of the zebrafish system to increase the understanding of the role of Gpr126 in Schwann cell myelination and illuminate the mechanisms controlling oligodendrocyte development and myelination. We also summarize similarities and differences between zebrafish radial glia and mammalian astrocytes and consider the possibility that their distinct characteristics may represent extremes in a continuum of cell identity. Finally, we focus on the emergence of zebrafish as a model for elucidating the development and function of microglia. These recent studies have highlighted the power of the zebrafish system for analyzing important aspects of glial development and function.

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Section: Oligodendrocytes During Injury and Diseasementioning

confidence: 99%

Glial Cell Development and Function in Zebrafish

Lyons

Talbot

2014

Cold Spring Harb Perspect Biol

125

100

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“…Here, we use zebrafish, which have recently become established as a powerful model for the study of glial cells and myelinated axons (Brosamle and Halpern, 2002;Buckley et al, 2010;Kazakova et al, 2006;Kirby et al, 2006;Li et al, 2007;Lyons et al, 2009;Monk et al, 2009;Pogoda et al, 2006;Takada and Appel, 2010), to study the role that axons play in regulating CNS myelination in vivo. As is the case in mammals, we show that single oligodendrocytes in zebrafish myelinate either a small number of large caliber axons or a larger number of smaller axons.…”

Section: Introductionmentioning

confidence: 99%

Individual axons regulate the myelinating potential of single oligodendrocytes in vivo

et al. 2011

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SUMMARYThe majority of axons in the central nervous system (CNS) are eventually myelinated by oligodendrocytes, but whether the timing and extent of myelination in vivo reflect intrinsic properties of oligodendrocytes, or are regulated by axons, remains undetermined. Here, we use zebrafish to study CNS myelination at single-cell resolution in vivo. We show that the large caliber Mauthner axon is the first to be myelinated (shortly before axons of smaller caliber) and that the presence of supernumerary large caliber Mauthner axons can profoundly affect myelination by single oligodendrocytes. Oligodendrocytes that typically myelinate just one Mauthner axon in wild type can myelinate multiple supernumerary Mauthner axons. Furthermore, oligodendrocytes that exclusively myelinate numerous smaller caliber axons in wild type can readily myelinate small caliber axons in addition to the much larger caliber supernumerary Mauthner axons. These data indicate that single oligodendrocytes can myelinate diverse axons and that their myelinating potential is actively regulated by individual axons.

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“…Tamoxifen and raloxifene were further studied, and the data generated indicated that their protective effects were not as a result of their known pharmacology; similar data were obtained for the other related active compounds. Clearly, the studies described here and others 47,48 in zebrafish, alongside those using C. elegans, 49,50 show the potential opportunity of these whole-organism multiwallbased phenotypic assays for drug repositioning.…”

Section: Drug Repositioning Through In Vitro Biological Screeningmentioning

confidence: 84%

In Vitro Screening for Drug Repositioning

Wilkinson

Pritchard

2015

SLAS Discovery

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Drug repositioning or repurposing has received much coverage in the scientific literature in recent years and has been responsible for the generation of both new intellectual property and investigational new drug submissions. The literature indicates a significant trend toward the use of computational-or informatics-based methods for generating initial repositioning hypotheses, followed by focused assessment of biological activity in phenotypic assays. Another viable method for drug repositioning is in vitro screening of known drugs or drug-like molecules, initially in disease-relevant phenotypic assays, to identify and validate candidates for repositioning. This approach can use large compound libraries or can focus on subsets of known drugs or drug-like molecules. In this short review, we focus on ways to generate and validate repositioning candidates in disease-related in vitro and phenotypic assays, and we discuss specific examples of this approach as applied to a variety of disease areas. We propose that in vitro screens offer several advantages over biochemical or in vivo methods as a starting point for drug repositioning.

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Drug reprofiling using zebrafish identifies novel compounds with potential pro-myelination effects

Cited by 73 publications

References 56 publications

Glial Cell Development and Function in Zebrafish

Glial Cell Development and Function in Zebrafish

Individual axons regulate the myelinating potential of single oligodendrocytes in vivo

In Vitro Screening for Drug Repositioning

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