Zebrafish models of Tauopathy.

Pittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh School of Medicine, PA, USA
Biochimica et Biophysica Acta (Impact Factor: 4.66). 03/2011; 1812(3):353-63. DOI: 10.1016/j.bbadis.2010.09.004
Source: PubMed

ABSTRACT Tauopathies are a group of incurable neurodegenerative diseases, in which loss of neurons is accompanied by intracellular deposition of fibrillar material composed of hyperphosphorylated forms of the microtubule-associated protein Tau. A zebrafish model of Tauopathy could complement existing murine models by providing a platform for genetic and chemical screens, in order to identify novel therapeutic targets and compounds with disease-modifying potential. In addition, Tauopathy zebrafish would be useful for hypothesis-driven experiments, especially those exploiting the potential to deploy in vivo imaging modalities. Several considerations, including conservation of specialized neuronal and other cellular populations, and biochemical pathways implicated in disease pathogenesis, suggest that the zebrafish brain is an appropriate setting in which to model these complex disorders. Novel transgenic zebrafish lines expressing wild-type and mutant forms of human Tau in CNS neurons have recently been reported. These studies show evidence that human Tau undergoes disease-relevant changes in zebrafish neurons, including somato-dendritic relocalization, hyperphosphorylation and aggregation. In addition, preliminary evidence suggests that Tau transgene expression can precipitate neuronal dysfunction and death. These initial studies are encouraging that the zebrafish holds considerable promise as a model in which to study Tauopathies. Further studies are necessary to clarify the phenotypes of transgenic lines and to develop assays and models suitable for unbiased high-throughput screening approaches. This article is part of a Special Issue entitled Zebrafish Models of Neurological Diseases.

  • Source
    Proteomics - Human Diseases and Protein Functions, Edited by Tsz Kwong Man, 02/2012: chapter The Microtubule-Dissociating Tau in Neurological Disorders: pages 291-326; InTech., ISBN: 978-953-307-832-8
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Rodent models have been extensively used to investigate the cause and mechanisms behind Alzheimer's disease. Despite many years of intensive research using these models we still lack a detailed understanding of the molecular events that lead to neurodegeneration. Although zebrafish lack the complexity of advanced cognitive behaviors evident in rodent models they have proven to be a very informative model for the study of human diseases. In this review we give an overview of how the zebrafish has been used to study Alzheimer's disease. Zebrafish possess genes orthologous to those mutated in familial Alzheimer's disease and research using zebrafish has revealed unique characteristics of these genes that have been difficult to observe in rodent models. The zebrafish is becoming an increasingly popular model for the investigation of Alzheimer's disease and will complement studies using other models to help complete our understanding of this disease.
    Frontiers in Genetics 06/2014; 5:189. DOI:10.3389/fgene.2014.00189
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Alzheimer's disease (AD) is emerging as the most prevalent and socially disruptive illness of aging populations, as more people live long enough to become affected. Although AD is placing a considerable and increasing burden on society, it represents the largest unmet medical need in neurology, because current drugs improve symptoms, but do not have profound disease-modifying effects. Although AD pathogenesis is multifaceted and difficult to pinpoint, genetic and cell biological studies led to the amyloid hypothesis, which posits that amyloid β (Aβ) plays a pivotal role in AD pathogenesis. Amyloid precursor protein (APP), as well as β- and γ-secretases are the principal players involved in Aβ production, while α-secretase cleavage on APP prevents Aβ deposition. The association of early onset familial AD with mutations in the APP and γ-secretase components provided a potential tool of generating animal models of the disease. However, a model that recapitulates all the aspects of AD has not yet been produced. Here, we face the problem of modeling AD pathology describing several models, which have played a major role in defining critical disease-related mechanisms and in exploring novel potential therapeutic approaches. In particular, we will provide an extensive overview on the distinct features and pros and contras of different AD models, ranging from invertebrate to rodent models and finally dealing with computational models and induced pluripotent stem cells.
    Frontiers in Pharmacology 06/2013; 4:77. DOI:10.3389/fphar.2013.00077


Available from