Calcium ions promote formation of amyloid β-peptide (1-40) oligomers causally implicated in neuronal toxicity of Alzheimer's disease.
Calcium ions promote formation of amyloid β-peptide (1-40) oligomers causally implicated in neuronal toxicity of Alzheimer's disease.
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钙离子促进形成淀粉样β肽（1-40）的寡聚物，该低聚物因果关系与阿尔茨海默氏病的神经元毒性有关。
DOI：
10.1371/journal.pone.0018250
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发表时间：
2011-03-28
期刊：
影响因子：
3.7
通讯作者：
Raussens V
中科院分区：
文献类型：
--
作者：
Itkin A;Dupres V;Dufrêne YF;Bechinger B;Ruysschaert JM;Raussens V
淀粉样β肽（Aβ）与阿尔茨海默病（AD）有直接关系。在其单体形式中，Aβ聚集以产生原纤维和一系列低聚物，后者是最具神经毒性的。在衰老的大脑和神经退行性疾病中，Ca 2+稳态的失调在许多过程中起着至关重要的作用，并导致细胞功能障碍和死亡。在此我们假设钙可以使或加速Aβ的聚集。我们比较了Aβ（1-40）和Aβ（1-40）E22 G的聚集模式，Aβ（1-40）E22 G是一种携带北极突变的淀粉样肽，可导致疾病的早期发作。我们发现，在Ca ~（2+）存在下，Aβ（1-40）优先形成类似于Aβ（1-40）E22 G在有或无Ca ~（2+）存在下形成的寡聚体，而在无Ca ~（2+）存在下，Aβ（1-40）聚集形成原纤维。通过接触模式原子力显微镜成像证实了低聚物的形态相似性。通过凝胶电泳和Western blot分析检测了不同样品中寡聚体和纤维状物质的分布，并通过硫磺素T荧光实验进一步证实了这一结果。在不含Ca 2+的样品中，傅里叶变换红外光谱显示低聚物从反平行β-折叠转化为原纤维的平行β-折叠构象特征。总之，这些结果使我们得出结论，钙离子刺激Aβ（1-40）寡聚体的形成，这与AD的发病机制有关。
Amyloid β-peptide (Aβ) is directly linked to Alzheimer's disease (AD). In its monomeric form, Aβ aggregates to produce fibrils and a range of oligomers, the latter being the most neurotoxic. Dysregulation of Ca2+ homeostasis in aging brains and in neurodegenerative disorders plays a crucial role in numerous processes and contributes to cell dysfunction and death. Here we postulated that calcium may enable or accelerate the aggregation of Aβ. We compared the aggregation pattern of Aβ(1–40) and that of Aβ(1–40)E22G, an amyloid peptide carrying the Arctic mutation that causes early onset of the disease. We found that in the presence of Ca2+, Aβ(1–40) preferentially formed oligomers similar to those formed by Aβ(1–40)E22G with or without added Ca2+, whereas in the absence of added Ca2+ the Aβ(1–40) aggregated to form fibrils. Morphological similarities of the oligomers were confirmed by contact mode atomic force microscopy imaging. The distribution of oligomeric and fibrillar species in different samples was detected by gel electrophoresis and Western blot analysis, the results of which were further supported by thioflavin T fluorescence experiments. In the samples without Ca2+, Fourier transform infrared spectroscopy revealed conversion of oligomers from an anti-parallel β-sheet to the parallel β-sheet conformation characteristic of fibrils. Overall, these results led us to conclude that calcium ions stimulate the formation of oligomers of Aβ(1–40), that have been implicated in the pathogenesis of AD.
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DOI：
10.1016/j.bbrc.2007.07.082
发表时间：
2007-10-05
影响因子：
3.1
作者：
Benseny-Cases, Nuria;Cocera, Mercedes;Cladera, Josep
通讯作者：
Cladera, Josep
影响因子：
4.8
作者：
Bucciantini, M;Calloni, G;Stefani, M
通讯作者：
Stefani, M
影响因子：
4.8
作者：
De Felice, Fernanda G.;Velasco, Pauline T.;Klein, William L.
通讯作者：
Klein, William L.
影响因子：
5.5
作者：
BLISS, TVP;LOMO, T
通讯作者：
LOMO, T
DOI：
10.1073/pnas.91.2.534
发表时间：
1994-01-18
影响因子：
11.1
作者：
ITO, E;OKA, K;ALKON, DL
通讯作者：
ALKON, DL