Shanghai Geriatric Institute of Chinese Medicine, Shanghai 200031, PR China.
Int J Neurosci. 2012 Jun;122(6):290-7. doi: 10.3109/00207454.2011.649867. Epub 2012 Feb 20.
Accumulation of the amyloid β protein (Aβ) in the brain is an important step in the pathogenesis of Alzheimer's disease. Many molecules could bind with Aβ, among which some molecules mediate Aβ neuronal toxicity. Thus, it is of interest to study the binding proteins of Aβ, and the functions that might be affected by Aβ. In the present study, we observed that accumulation of α-subunit of ATP synthase is associated with aggregates of Aβ proteins in amyloid plaques of amyloid precursor protein/presennillin-1 transgenic mice, and identified the α-subunit of ATP synthase as one of the Aβ binding proteins on the plasma membrane of neural cells by Western blot and mass spectrometry. In order to evaluate the consequences of the interaction between Aβ and surface α-subunit of ATP synthase, the extracellular ATP generation was analyzed, which showed that aggregated Aβ partially inhibited the extracellular generation of ATP, but was unable to significantly induce a decrease in cell surface ATP synthase α on neurons. These results suggest that the cell surface ATP synthase α is a binding protein for Aβ on neural cells, the functional inhibition of surface ATP synthase might be involved in machinery of brain malfunction in Aβ-mediated pathogenesis of Alzheimer's disease.
淀粉样β蛋白（Aβ）在脑内的沉积是阿尔茨海默病发病机制中的一个重要步骤。许多分子可以与 Aβ结合，其中一些分子介导 Aβ 的神经元毒性。因此，研究 Aβ的结合蛋白以及可能受 Aβ影响的功能很有意义。在本研究中，我们观察到在淀粉样前体蛋白/早老素-1转基因小鼠的淀粉样斑块中，ATP 合酶α亚基的积累与 Aβ蛋白的聚集有关，并通过 Western blot 和质谱鉴定了 ATP 合酶α亚基是神经细胞膜上的 Aβ结合蛋白之一。为了评估 Aβ与质膜表面 ATP 合酶α亚基之间相互作用的后果，我们分析了细胞外 ATP 的生成情况，结果表明聚集的 Aβ部分抑制了细胞外 ATP 的生成，但不能显著诱导神经元表面 ATP 合酶α亚基的减少。这些结果表明，质膜表面 ATP 合酶α亚基是神经细胞 Aβ的结合蛋白，表面 ATP 合酶的功能抑制可能参与 Aβ介导的阿尔茨海默病发病机制中的脑功能障碍机制。
