Multiple signaling factors and drugs alleviate neuronal death induced by expression of human and zebrafish tau proteins in vivo

Journal of Biomedical Science

Research

Rey-Yue Yuan¹  Chin-Chun Hung²  Rita Pei-Yeh Chen²  Chang-Jen Huang²  Chun-Che Chang³  Bo-Kai Wu⁴  Yung-Feng Liao⁵  Pung-Pung Hwang⁵  Huang-Wei Lien⁵ 

[1]Department of Neurology, School of Medicine, College of Medicine, Taipei Medical University, 110, Taipei, Taiwan

[2]Institute of Biological Chemistry, Academia Sinica, 128 Academia Rd., Sec. 2, 115, Taipei, Taiwan

[3]Institute of Biotechnology, National Taiwan University, 106, Taipei, Taiwan

[4]Department of Entomology, National Taiwan University, 106, Taipei, Taiwan

[5]Institute of Biotechnology, National Taiwan University, 106, Taipei, Taiwan

[6]Institute of Biological Chemistry, Academia Sinica, 128 Academia Rd., Sec. 2, 115, Taipei, Taiwan

[7]Institute of Cellular and Organismic Biology, Academia Sinica, 115, Taipei, Taiwan

关键词: Tauopathy;    Bcl2-L1;    Nrf2;    Neurotoxicity;    GDNF;    Zebrafish;   

DOI  :  10.1186/s12929-016-0237-4

 received in 2015-08-31, accepted in 2016-01-20,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundThe 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.ResultsTransgenic 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.ConclusionsThe 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.

【 授权许可】

CC BY   
© Wu et al. 2016