氧化应激
神经毒性
化学
淀粉样前体蛋白
药理学
炎症
乙酰胆碱酯酶
淀粉样蛋白(真菌学)
发病机制
转基因小鼠
活性氧
生物化学
细胞生物学
阿尔茨海默病
转基因
生物
毒性
内科学
免疫学
医学
疾病
酶
基因
无机化学
有机化学
作者
Chun-ling Su,Yusi Chen,Kelin Chen,Wei Li,Huang Tang
标识
DOI:10.1016/j.neuint.2020.104794
摘要
Cu2+ plays a key role in the pathogenesis of Alzheimer's disease (AD). The dysregulation of Cu2+ can cause neuronal damage and aggravate development of AD. Moreover, a series of 4-substituted sampangine derivatives have been investigated as inhibitors of acetylcholinesterase and β-amyloid (Aβ) aggregation for the treatment of AD in our previous studies. In the present study, we reported that one of these derivatives SD-1 was able to modulate Cu2+-mediated multiple pathological elements in AD. The high selectivity of SD-1 for Cu2+ over other biologically relevant metal ions was demonstrated by ITC. Western blotting analysis, light-scattering study, DCF-DA assay and paralysis experiment indicated that SD-1 suppressed the formation of Cu2+-Aβ species, alleviated the Cu2+-Aβ species induced neurotoxicity and inhibited the production of ROS catalyzed by Cu2+-Aβ species in SH-SY5Y cells over-expressing the Swedish mutant form of human APP (APPsw SH-SY5Y) and Aβ42 transgenic C elegans (CL2020). Furthermore, SD-1 inhibited the expressions of NO, iNOS, TNF-α, IL-1β and IL-6 induced by Cu2+ in BV2 microglial cells. Collectively, these findings provided valuable insights into the design and development of potent metal-chelating agents for AD treatment.
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