Fang Chuan-Lin, Wu Wei-Hui, Liu Qian, Sun Xun, Ma Yuan, Zhao Yu-Fen, Li Yan-Mei
Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology, Ministry of Education, Department of Chemistry, Tsinghua University, Beijing, PR China.
Regul Pept. 2010 Aug 9;163(1-3):1-6. doi: 10.1016/j.regpep.2010.05.001. Epub 2010 May 15.
Amyloid-beta (Abeta) aggregation and Cu(II)-related oxidative stress are involved in the dysfunction and death of neurons in Alzheimer's disease (AD). However, the relationship between Abeta and Cu(II) is not clear. Furthermore, the pro- or anti-oxidant properties of Abeta are also under great debate. Here the H2O2 generating ability of Abeta42 in its monomeric, oligomeric and fibrillar forms was studied in the presence of Cu(II). The results show that Abeta42 in both oligomeric and fibrillar forms can promote H2O2 generation at lower concentrations of Cu(II) and Abeta42 oligomer can promote H2O2 generation to a higher extent. Nevertheless, the promoting effect of Abeta42 oligomer and fibril may convert to an inhibitory effect when the concentration of Cu(II) is increased. This indicates the dual functions of Abeta42 oligomer and fibril in Cu(II)-induced H2O2 production. Hereby we present a new perspective on the roles of Abeta42 in Cu(II)-mediated oxidative stress and add new evidence to the viewpoint that Abeta42 oligomer may be primarily responsible for the pathogenesis of AD.
淀粉样β蛋白（Aβ）聚集和铜（II）相关的氧化应激参与了阿尔茨海默病（AD）中神经元的功能障碍和死亡。然而，Aβ与铜（II）之间的关系尚不清楚。此外，Aβ的促氧化或抗氧化特性也存在很大争议。在此研究了在铜（II）存在的情况下，单体、寡聚体和纤维状形式的Aβ42产生过氧化氢的能力。结果表明，寡聚体和纤维状形式的Aβ42在较低浓度的铜（II）下均可促进过氧化氢的产生，且Aβ42寡聚体促进过氧化氢产生的程度更高。然而，当铜（II）浓度增加时，Aβ42寡聚体和纤维的促进作用可能会转变为抑制作用。这表明Aβ42寡聚体和纤维在铜（II）诱导的过氧化氢产生中具有双重功能。据此，我们对Aβ42在铜（II）介导的氧化应激中的作用提出了新的观点，并为Aβ42寡聚体可能是AD发病机制的主要原因这一观点增添了新证据。
