Toggle Main Menu Toggle Search

Open Access padlockePrints

Zebrafish as an animal model for drug discovery in Parkinson's disease and other movement disorders: A systematic review

Lookup NU author(s): Professor Tiago Outeiro

Downloads


Licence

This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 2018 Vaz, Outeiro and Ferreira. Movement disorders can be primarily divided into hypokinetic and hyperkinetic. Most of the hypokinetic syndromes are associated with the neurodegenerative disorder Parkinson's disease (PD). By contrast, hyperkinetic syndromes encompass a broader array of diseases, including dystonia, essential tremor, or Huntington's disease. The discovery of effective therapies for these disorders has been challenging and has also involved the development and characterization of accurate animal models for the screening of new drugs. Zebrafish constitutes an alternative vertebrate model for the study of movement disorders. The neuronal circuitries involved in movement in zebrafish are well characterized, and most of the associated molecular mechanisms are highly conserved. Particularly, zebrafish models of PD have contributed to a better understanding of the role of several genes implicated in the disease. Furthermore, zebrafish is a vertebrate model particularly suited for large-scale drug screenings. The relatively small size of zebrafish, optical transparency, and lifecycle, are key characteristics that facilitate the study of multiple compounds at the same time. Several transgenic, knockdown, and mutant zebrafish lines have been generated and characterized. Therefore, it is central to critically analyze these zebrafish lines and understand their suitability as models of movement disorders. Here, we revise the pathogenic mechanisms, phenotypes, and responsiveness to pharmacotherapies of zebrafish lines of the most common movement disorders. A systematic review of the literature was conducted by including all studies reporting the characterization of zebrafish models of the movement disorders selected from five bibliographic databases. A total of 63 studies were analyzed, and the most relevant data within the scope of this review were gathered. The majority (62%) of the studies were focused in the characterization of zebrafish models of PD. Overall, the zebrafish models included display conserved biochemical and neurobehavioral features of the phenomenology in humans. Nevertheless, in light of what is known for all animal models available, the use of zebrafish as a model for drug discovery requires further optimization. Future technological developments alongside with a deeper understanding of the molecular bases of these disorders should enable the development of novel zebrafish lines that can prove useful for drug discovery for movement disorders.


Publication metadata

Author(s): Vaz RL, Outeiro TF, Ferreira JJ

Publication type: Review

Publication status: Published

Journal: Frontiers in Neurology

Year: 2018

Volume: 9

Online publication date: 01/06/2018

Acceptance date: 30/04/2018

ISSN (electronic): 1664-2295

Publisher: Frontiers Media S.A.

URL: https://doi.org/10.3389/fneur.2018.00347

DOI: 10.3389/fneur.2018.00347


Actions

Find at Newcastle University icon    Link to this publication


Share