Secreted Aβ Does Not Mediate Neurotoxicity by Antibody-Stimulated Amyloid Precursor Protein
Secreted Aβ Does Not Mediate Neurotoxicity by Antibody-Stimulated Amyloid Precursor Protein
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分泌的 Aβ 不会介导抗体刺激的淀粉样前体蛋白的神经毒性
DOI：
10.1006/bbrc.2001.4604
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发表时间：
2001
影响因子：
3.1
通讯作者：
I. Nishimoto
中科院分区：
文献类型：
--
作者：
H. Sudo;Y. Hashimoto;T. Niikura;Z. Shao;T. Yasukawa;Y. Ito;M. Yamada;M. Hata;T. Hiraki;M. Kawasumi;K. Kouyama;I. Nishimoto
APP（沉积在阿尔茨海默病大脑中的 Abeta 前体）的抗体已被证明会导致神经元死亡。因此，确定 Abeta 是否介导抗体诱导的神经毒性非常重要。当用抗 APP 抗体处理原代神经元时，能够检测 100 nM Abeta 肽的测定无法检测到培养基中的 Abeta40 和 Abeta42。然而，外源处理的 Abeta1-42 或 Abeta1-43 需要 >3 microM 才能发挥神经毒性，而 25 microM Abeta1-40 则不具有神经毒性。谷胱甘肽乙酯抑制抗 APP 抗体引起的神经元死亡，但不抑制 Abeta1-42 引起的神经元死亡，而血清减弱 Abeta1-42 引起的毒性，但不抑制抗 APP 抗体引起的神经元死亡。使用永生化神经元细胞，我们指定负责毒性的结构域是 APP 的细胞质 His(657)-Lys(676)，而不是 Abeta1-42 区域。这表明抗APP抗体引起的神经元细胞死亡不是由分泌的Abeta介导的。
Antibodies against APP, a precursor of Abeta deposited in Alzheimer's disease brain, have been shown to cause neuronal death. Therefore, it is important to determine whether Abeta mediates antibody-induced neurotoxicity. When primary neurons were treated with anti-APP antibodies, Abeta40 and Abeta42 in the cultured media were undetectable by an assay capable of detecting 100 nM Abeta peptides. However, exogenously treated Abeta1-42 or Abeta1-43 required >3 microM to exert neurotoxicity, and 25 microM Abeta1-40 was not neurotoxic. Glutathione-ethyl-ester inhibited neuronal death by anti-APP antibody, but not death by Abeta1-42, whereas serum attenuated toxicity by Abeta1-42, but not by anti-APP antibody. Using immortalized neuronal cells, we specified the domain responsible for toxicity to be cytoplasmic His(657)-Lys(676), but not the Abeta1-42 region, of APP. This indicates that neuronal cell death by anti-APP antibody is not mediated by secreted Abeta.
影响因子：
56.9
作者：
BUSH, AI;PETTINGELL, WH;TANZI, RE
通讯作者：
TANZI, RE
DOI：
10.1073/pnas.90.17.7951
发表时间：
1993-09-01
影响因子：
11.1
作者：
LOO, DT;COPANI, A;COTMAN, CW
通讯作者：
COTMAN, CW