https://scholars.lib.ntu.edu.tw/handle/123456789/395963
Title: | Multiple signaling factors and drugs alleviate neuronal death induced by expression of human and zebrafish tau proteins in vivo | Authors: | Wu, B.-K. Yuan, R.-Y. Lien, H.-W. Hung, C.-C. Hwang, P.-P. Chen, R.P.-Y. CHUN-CHE CHANG Liao, Y.-F. Huang, C.-J. |
Keywords: | Bcl2-L1; GDNF; Neurotoxicity; Nrf2; Tauopathy; Zebrafish | Issue Date: | 2016 | Journal Volume: | 23 | Journal Issue: | 1 | Source: | Journal of Biomedical Science | Abstract: | Background: The axonal tau protein is a tubulin-binding protein, which plays important roles in the formation and stability of the microtubule. Mutations in the tau gene are associated with familial forms of frontotemporal dementia with Parkinsonism linked to chromosome-17 (FTDP-17). Paired helical filaments of tau and extracellular plaques containing beta-amyloid are found in the brain of Alzheimer's disease (AD) patients. Results: Transgenic models, including those of zebrafish, have been employed to elucidate the mechanisms by which tau protein causes neurodegeneration. In this study, a transient expression system was established to express GFP fusion proteins of zebrafish and human tau under the control of a neuron-specific HuC promoter. Approximately ten neuronal cells expressing tau-GFP in zebrafish embryos were directly imaged and traced by time-lapse recording, in order to evaluate the neurotoxicity induced by tau-GFP proteins. Expression of tau-GFP was observed to cause high levels of neuronal death. However, multiple signaling factors, such as Bcl2-L1, Nrf2, and GDNF, were found to effectively protect neuronal cells expressing tau-GFP from death. Treatment with chemical compounds that exert anti-oxidative or neurotrophic effects also resulted in a similar protective effect and maintained human tau-GFP protein in a phosphorylated state, as detected by antibodies pT212 and AT8. Conclusions: The novel finding of this study is that we established an expression system expressing tau-GFP in zebrafish embryos were directly imaged and traced by time-lapse recording to evaluate the neurotoxicity induced by tau-GFP proteins. This system may serve as an efficient in vivo imaging platform for the discovery of novel drugs against tauopathy. ? 2016 Wu et al. |
URI: | http://www.scopus.com/inward/record.url?eid=2-s2.0-84957605816&partnerID=MN8TOARS http://scholars.lib.ntu.edu.tw/handle/123456789/395963 |
DOI: | 10.1186/s12929-016-0237-4 | SDG/Keyword: | AT8 antibody; biological factor; cell protein; glial cell line derived neurotrophic factor; green fluorescent protein; hybrid protein; protein antibody; protein Bcl2 L1; pT212 antibody; signaling factor; tau protein; transcription factor Nrf2; unclassified drug; MAPT protein, human; tau protein; tau protein, zebrafish; zebrafish protein; animal cell; animal tissue; antioxidant activity; Article; controlled study; embryo; gene expression system; human; in vivo study; intracellular recording; intracellular signaling; nerve cell necrosis; nerve degeneration; neuroprotection; neurotoxicity; nonhuman; priority journal; promoter region; protein analysis; protein expression; protein function; protein phosphorylation; tauopathy; time lapse imaging; transgenic zebrafish; transient expression; animal; cell death; chromosome 17; disease model; frontotemporal dementia; genetics; metabolism; nerve cell; nonmammalian embryo; pathology; transgenic animal; zebra fish; Animals; Animals, Genetically Modified; Cell Death; Chromosomes, Human, Pair 17; Disease Models, Animal; Embryo, Nonmammalian; Frontotemporal Dementia; Humans; Neurons; tau Proteins; Zebrafish; Zebrafish Proteins |
Appears in Collections: | 昆蟲學系 |
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