کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5534709 | 1551267 | 2017 | 45 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Oxoisoaporphine alkaloid derivative 8-1 reduces Aβ1-42 secretion and toxicity in human cell and Caenorhabditis elegans models of Alzheimer's disease
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
بیولوژی سلول
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چکیده انگلیسی
Alzheimer's disease (AD) is a multifactorial neurodegenerative disease and a growing health problem worldwide. Because the drugs currently used to treat AD have certain drawbacks such as single targeting, there is a need to develop novel multi-target compounds, among which oxoisoaporphine alkaloid derivatives are promising candidates. In this study, the possible anti-AD activities of 14 novel oxoisoaporphine alkaloid derivatives that we synthesized were screened and evaluated. We found that, in the 14 novel derivatives, compound 8-1 significantly reduced Aβ1-42 secretion in SH-SY5Y cells overexpressing the Swedish mutant form of human β-amyloid precursor protein (APPsw). Next, we found that compound 8-1 could down-regulate the expression level of β-amyloid precursor protein (APP) in APPsw cells. Moreover, compound 8-1 significantly delayed paralysis in the Aβ1-42-transgenic Caenorhabditis elegans strain GMC101, which could be explained by the fact that compound 8-1 down-regulated acetylcholinesterase activity, protected against H2O2-induced acute oxidative stress and paraquat-induced chronic oxidative stress, and enhanced autophagy activity. Taken together, our data suggest that compound 8-1 could attenuate the onset and development of AD.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurochemistry International - Volume 108, September 2017, Pages 157-168
Journal: Neurochemistry International - Volume 108, September 2017, Pages 157-168
نویسندگان
Liyingzi Huang, Yunfeng Luo, Zhijun Pu, Xianghui Kong, Xiang Fu, Huanhuan Xing, Shenqi Wei, Wei Chen, Huang Tang,