AMPA受体的移除是β淀粉样蛋白诱导的突触抑制和树突棘丢失的基础。
AMPAR removal underlies Abeta-induced synaptic depression and dendritic spine loss.
作者信息
Hsieh Helen, Boehm Jannic, Sato Chihiro, Iwatsubo Takeshi, Tomita Taisuke, Sisodia Sangram, Malinow Roberto
机构信息
Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
出版信息
Neuron. 2006 Dec 7;52(5):831-43. doi: 10.1016/j.neuron.2006.10.035.
Abstract
Beta amyloid (Abeta), a peptide generated from the amyloid precursor protein (APP) by neurons, is widely believed to underlie the pathophysiology of Alzheimer's disease. Recent studies indicate that this peptide can drive loss of surface AMPA and NMDA type glutamate receptors. We now show that Abeta employs signaling pathways of long-term depression (LTD) to drive endocytosis of synaptic AMPA receptors. Synaptic removal of AMPA receptors is necessary and sufficient to produce loss of dendritic spines and synaptic NMDA responses. Our studies indicate the central role played by AMPA receptor trafficking in Abeta-induced modification of synaptic structure and function.
摘要
β淀粉样蛋白（Aβ）是一种由神经元中的淀粉样前体蛋白（APP）产生的肽，人们普遍认为它是阿尔茨海默病病理生理学的基础。最近的研究表明，这种肽会导致表面AMPA和NMDA型谷氨酸受体的丧失。我们现在发现，Aβ利用长时程抑制（LTD）的信号通路来驱动突触AMPA受体的内吞作用。AMPA受体的突触清除对于产生树突棘和突触NMDA反应的丧失是必要且充分的。我们的研究表明，AMPA受体转运在Aβ诱导的突触结构和功能改变中起着核心作用。
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