Zebrafish models of Tauopathy

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1812

Review

Bai, Qing^1,2  Burton, Edward A.^1,2,3,4,5,6 

[1] Univ Pittsburgh, Sch Med, Pittsburgh Inst Neurodegenerat Dis, Pittsburgh, PA 15260 USA

[2] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15260 USA

[3] Univ Pittsburgh, Sch Med, Dept Microbiol & Mol Genet, Pittsburgh, PA 15260 USA

[4] Univ Pittsburgh, Med Ctr, Div Movement Disorders, Pittsburgh, PA 15260 USA

[5] VA Pittsburgh Healthcare Syst, Dept Neurol, Pittsburgh, PA USA

[6] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA

关键词: Tau;    Tauopathy;    Progressive supranuclear palsy;    Zebrafish;    Alzheimer's disease;    Transgenic;    Neurodegeneration;   

DOI  :  10.1016/j.bbadis.2010.09.004

来源: Elsevier

【 摘 要 】

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. Published by Elsevier B.V.

【 授权许可】

Free