Transgenic zebrafish models of neurodegenerative diseases

Abstract

Since the introduction of the zebrafish as a model for the study of vertebrate developmental biology, an extensive array of techniques for its experimental manipulation and analysis has been developed. Recently it has become apparent that these powerful methodologies might be deployed in order to elucidate the pathogenesis of human neurodegenerative diseases and to identify candidate therapeutic approaches. In this article, we consider evidence that the zebrafish central nervous system provides an appropriate setting in which to model human neurological disease and we review techniques and resources available for generating transgenic models. We then examine recent publications showing that appropriate phenotypes can be provoked in the zebrafish through transgenic manipulations analogous to genetic abnormalities known to cause human tauopathies, polyglutamine diseases or motor neuron degenerations. These studies show proof of concept that findings in zebrafish models can be applicable to the pathogenic mechanisms underlying human diseases. Consequently, the prospects for providing novel insights into neurodegenerative diseases by exploiting transgenic zebrafish models and discovery-driven approaches seem favorable.