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可溶性Aβ寡聚体被认为是引起AD早期阶段突触功能失常的最主要因素。不同的NMDA受体亚单位均与Aβ诱导的突触毒性有密切关系。在目前的研究中,我们发现Aβ选择性的诱导了NR2B亚单位蛋白水平的下降,但是NR1,NR2A及SAP102的蛋白表达并没有显著改变。这些结果提示NR2B在Aβ急性处理后导致的早期突触毒性作用中变化更引人关注。而且,我们还惊奇的发现,Aβ诱导了突触内NR2A和SAP102的puncta密度明显减少,这进一步提示Aβ急性处理后突触内外NMDA受体亚单位发生了复杂的改变。我们的研究结果表明在AD早期阶段,Aβ对于不同的NMDA受体亚单位及突触相关蛋白的产生了极其复杂的效应。这也在某种程度上解释了为什么临床上难于寻找适合的与AD早期NMDA受体功能异常相关的阻止突触功能失常和突触缺失的药物。
Soluble Aβ oligomers are thought to be the most important factor causing synaptic dysfunction in early stages of AD. Different NMDA receptor subunits are closely related to Aβ-induced synaptic toxicity. In the present study, we found that Aβ selectively induced a decrease in NR2B subunit protein levels, but that of NR1, NR2A and SAP102 did not change significantly. These results suggest that changes in NR2B in the early synaptic toxicity caused by A [beta] acute treatment are more interesting. Moreover, we were also surprised to find that Aβ induced a marked decrease in puncta density in synaptic NR2A and SAP102, further suggesting that complex changes occur in the synaptic NMDA receptor subunits after Aβ acute treatment. Our results show that Aβ has an extremely complex effect on different NMDA receptor subunits and synapto-related proteins in the early stages of AD. This also explains to some extent why it is clinically difficult to find suitable drugs to prevent synaptic dysfunction and synaptic loss associated with dysfunction of early NMDA receptors in AD.