- 作者: Bo-Kai Wu, Rey-Yue Yuan, Huang-Wei Lien, Chin-Chun Hung, Pung-Pung Hwang, Rita Pei-Yeh Chen, Chun-Che Chang, Yung-Feng Liao and Chang-Jen Huang
- 作者服務機構: Institute of Biotechnology, National Taiwan University, Taipei 106, Taiwan
- 中文摘要: --
- 英文摘要:
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. - 中文關鍵字: --
- 英文關鍵字: Tauopathy, Bcl2-L1, Nrf2, Neurotoxicity, GDNF, Zebrafish