文章基本信息

标题：Synaptic transmission block by presynaptic injection of oligomeric amyloid beta
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作者：Herman Moreno ; Eunah Yu ; Gustavo Pigino 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2009
卷号：106
期号：14
页码：5901-5906
DOI：10.1073/pnas.0900944106
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Early Alzheimer's disease (AD) pathophysiology is characterized by synaptic changes induced by degradation products of amyloid precursor protein (APP). The exact mechanisms of such modulation are unknown. Here, we report that nanomolar concentrations of intraaxonal oligomeric (o)A{beta}42, but not oA{beta}40 or extracellular oA{beta}42, acutely inhibited synaptic transmission at the squid giant synapse. Further characterization of this phenotype demonstrated that presynaptic calcium currents were unaffected. However, electron microscopy experiments revealed diminished docked synaptic vesicles in oA{beta}42-microinjected terminals, without affecting clathrin-coated vesicles. The molecular events of this modulation involved casein kinase 2 and the synaptic vesicle rapid endocytosis pathway. These findings open the possibility of a new therapeutic target aimed at ameliorating synaptic dysfunction in AD.
关键词：Alzheimer's disease ; fluorescence microscopy ; presynaptic voltage clamp ; squid giant synapse ; ultrastructure