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


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.

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    • "Diseases with tau-like pathology are collectively termed “tauopathies.” A review by Bai and Burton (2011) discussed how the zebrafish has been used to investigate these diseases. A number of MAPT protein isoforms exist as a result of alternative splicing of MAPT transcripts. "
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    Frontiers in Genetics 06/2014; 5:189. DOI:10.3389/fgene.2014.00189
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    • "Application of inhibitors of human GSK3β reduced tau phosphorylation showing that zebrafish kinases are sufficiently conserved with respect to their human orthologues. Current evidence point out that zebrafish tau models recapitulate pathological and biochemical events that occur in tauopathies and therefore may be useful tools for further studies in the aetiology of dementia (Bai Q and Burton EA, 2011). "
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    ABSTRACT: Zebrafish is rapidly emerging as a promising model organism to study various central nervous system (CNS) disorders, including Alzheimer's disease (AD). AD is the main cause of dementia in the human population and there is an urgency to understand the causes of this neurodegenerative disease. In this respect, the development of new animal models to study the underlying neurodegenerative mechanisms of AD is an urgent need. In this review we analyze the current situation in the use of zebrafish as a model for AD, discussing the reasons to use this experimental paradigm in CNS investigation and analyzing the several strategies adopted to induce an AD-like pathology in zebrafish. We discuss the strategies of performing interventions to cause damage in the zebrafish brain by altering the major neurotransmitter systems (such as cholinergic, glutamatergic or GABAergic circuits). We also analyze the several transgenic zebrafish constructed for the AD study, discussing both the familial-AD models based on APP processing pathway (APP and presenilins) and in the TAU hyperphosphorylation, together with the genes involved in sporadic-AD, as apolipoprotein E. We conclude that zebrafish is in a preliminary stage of development in the AD field, and that the transgenic animals must be improved to use this fish as an optimal model for AD research. Furthermore, a deeper knowledge of the zebrafish brain and a better characterization of the injury caused by alterations in the major neurotransmitter systems are needed.
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