A novel transgenic zebrafish sensor for screening of potential therapeutic drug for Parkinson diseas

来源 :中国药理学会第十三次全国学术大会 | 被引量 : 0次 | 上传用户:skyaixiao
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  The sensitive tyrosine hydroxylasegreen fluorescent protein (THGFP) transgenic zebrafish was originally developed and applied as a biosensor to assessments of the effects of addict drugs in our previous study.In this study, we found that the transgenic zebrafish unexpectedly be employed as an in vivo model to evaluate the neuroprotective effects of drug candidate for neurodegenerative disorder.Magnolol as predicted target owning to it rescued the deficit of motor behavior and restored TH loss in THGFP transgenic zebrafish after 250 μM 6OHDA toxin insult.Subsequently, we challenge SHSY5Y cells with 6OHDA as an in vitro model to confirm the neuroprotective effects of magnolol and discover the underlying mechanisms.Our results demonstrate magnolol prevented 6OHDAinduced reduction of cell viability in SHSY5Y cells; it also significantly attenuated 6OHDA induced apoptosis characterized by DNA fragmentation and caspase3 activation.Furthermore, Western blot analysis showed magnolol inhibited 6OHDA induced activation of p38, JNK and ERK mitogenactivated protein kinases (MAPK) signaling in SHSYSY cells.These results indicate magnolol may be useful as a potential therapeutic agent for the treatment of dopaminergic neuronal diseases.Importantly, we outspread transgenic zebrafish as a novel highthroughput live biosensor for screening drugs of Parkinson disease (PD).
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