Alzheimer’s disease (AD) and Type 2 Diabetes mellitus (T2Dm), two of the most common amyloidogenic diseases. They share a common pathological symptom, i.e., the formation of amyloid deposits comprised of amyloid β and amylin peptides, respectively. Autopsy of brains of AD-affected patients shows the presence of abnormally high concentrations of Cu in the deposited amyloid β plaques, while a significantly higher level of Cu is found in the serum of patients suffering from T2Dm. These invoke that Cu might play a crucial role in the onset of both AD and T2Dm. In fact, Cu is found to bind amyloid β as well as amylin relevant to AD and T2Dm, respectively. Cu–Aβ and Cu–amylin in their reduced states can generate partially reduced oxygen species (PROS) on reaction with O₂ which leads to oxidative stress in the brain and in the pancreas, respectively. However, the pathway of O₂ reduction is quite different for the two complexes. Moreover, the use of various spectroscopic techniques such as absorption, EPR, and CD involving native and site-directed mutants of the peptides show that their active-site environments are also dissimilar. Here, we have discussed the different aspects of Cu–Aβ and Cu–amylin complexes including their pH-dependent coordination environments and their reactivity towards O₂ which may be responsible for the oxidative stress associated with the two diseases. This depicts the significance of the Cu bound peptide complexes in the context of AD and T2Dm.Graphic abstract

中文翻译：

---

Cu结合的淀粉样蛋白β和淀粉样蛋白肽的活性位点环境。

阿尔茨海默氏病（AD）和2型糖尿病（T2Dm），这是两种最常见的淀粉样变性疾病。它们具有共同的病理症状，即分别由淀粉样蛋白β和淀粉样蛋白肽组成的淀粉样沉积物的形成。患有AD的患者的脑部解剖显示，在沉积的淀粉样β斑块中存在异常高浓度的Cu，而在患有T2Dm的患者的血清中发现明显更高的Cu水平。这些提示铜可能在AD和T2Dm的发作中起关键作用。实际上，发现Cu分别结合与AD和T2Dm有关的淀粉样蛋白β和淀粉样蛋白。处于还原态的Cu–Aβ和Cu–amylin在与O ₂反应时可产生部分还原的氧物种（PROS）分别导致大脑和胰腺的氧化应激。但是，两种配合物的O ₂还原途径截然不同。而且，使用各种光谱技术，例如吸收，EPR和CD涉及肽的天然和定点突变体，表明它们的活性位点环境也不相同。在这里，我们讨论了Cu-Aβ和​​Cu-amylin配合物的不同方面，包括它们的pH依赖性配位环境以及它们对O ₂的反应性，这可能是与这两种疾病相关的氧化应激的原因。这描绘了在AD和T2Dm的情况下Cu结合的肽复合物的重要性。图形摘要