血红素-Cu结合的aβ:光谱特征,反应性和与阿尔茨海默病相关性
Debajyoti Pramanik1, Chandradeep Ghosh, Somdatta Ghosh Dey
1Department of Inorganic Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Kolkata, India 700032.
Journal of the American Chemical Society
|August 30, 2011
概括
胺ββ (Aβ) 结合铜和血,形成复合物,产生有毒的活性氧物种. 这些heme-Cu-Aβ复合体显示出显著的过氧化酶活性,可能导致阿尔茨海默病的发病.
科学领域:
- 生物化学 生物化学
- 神经科学是一个神经科学.
- 氧化压力是一种氧化压力.
背景情况:
- 血与粉样β (Aβ) 的结合与阿尔茨海默氏症 (AD) 病原发生有关.
- 铜 (Cu) 和血红素与Aβ的同时结合是AD进展的关键因素.
研究的目的:
- 研究Aβ与Cu和heme共因子的结合相互作用.
- 阐明这些协因子-Aβ复合物的功能后果,特别是它们的过氧化酶活性和在活性氧物种生成中的作用.
主要方法:
- 用光谱和电化学分析来描述Aβ辅因子相互作用.
- 用酶动力学来评估Aβ复合物的过氧化酶活性.
主要成果:
- Aβ同时结合Cu和heme,而辅助因子在电子上保持不结合.
- 结合阻止了与Cu同时协调的histidine,反驳了以前的模型.
- 血红-Aβ和血红-Cu-Aβ复合体表现出显著的过氧化酶活性,将O(2) 降低为H(2) O(2).
- 与β结合的Cu也表现出过氧化酶活性.
- Aβ的Tyr10残留物为产生活性氧物种 (ROS) 捐赠电子,这种残留物在耐AD的动物中不存在.
- 血红素-Cu-Aβ复合体产生最大量的有毒ROS.
结论:
- Aβ可以结合和铜,形成功能性过氧化酶复合体.
- 这些复合物,特别是血红素-Cu-Aβ,通过产生ROS,促进阿尔茨海默病的氧化应激.
- 这些发现提供了对AD进展背后的分子机制的新见解,并突出了潜在的治疗点.
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