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首页> 外文期刊>Neuron >Deleterious effects of amyloid beta oligomers acting as an extracellular scaffold for mGluR5.
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Deleterious effects of amyloid beta oligomers acting as an extracellular scaffold for mGluR5.

机译：淀粉样β低聚物作为mGluR5的细胞外支架的有害作用。

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摘要

Soluble oligomers of amyloid beta (Abeta) play a role in the memory impairment characteristic of Alzheimer's disease. Acting as pathogenic ligands, Abeta oligomers bind to particular synapses and perturb their function, morphology, and maintenance. Events that occur shortly after oligomer binding have been investigated here in live hippocampal neurons by single particle tracking of quantum dot-labeled oligomers and synaptic proteins. Membrane-attached oligomers initially move freely, but their diffusion is hindered markedly upon accumulation at synapses. Concomitantly, individual metabotropic glutamate receptors (mGluR5) manifest strikingly reduced lateral diffusion as they become aberrantly clustered. This clustering of mGluR5 elevates intracellular calcium and causes synapse deterioration, responses prevented by an mGluR5 antagonist. As expected, clustering by artificial crosslinking also promotes synaptotoxicity. These results reveal a mechanism whereby Abeta oligomers induce the abnormal accumulation and overstabilization of a glutamate receptor, thus providing a mechanistic and molecular basis for Abeta oligomer-induced early synaptic failure.
机译：淀粉样β（Abeta）的可溶性低聚物在阿尔茨海默氏病的记忆障碍特征中发挥作用。作为致病性配体，Abeta低聚物与特定的突触结合并扰乱其功能，形态和维持。寡聚体结合后不久发生的事件已通过量子点标记的寡聚体和突触蛋白的单粒子追踪在活海马神经元中进行了研究。膜连接的低聚物起初自由移动，但在突触上积累时明显阻碍了它们的扩散。随之而来的是，单个代谢型谷氨酸受体（mGluR5）异常聚集时，其横向扩散显着降低。 mGluR5的这种簇集提高了细胞内钙的含量，并导致突触恶化，这是mGluR5拮抗剂阻止的。如所期望的，通过人工交联的聚集也促进突触毒性。这些结果揭示了一种机制，其中Abeta低聚物诱导谷氨酸受体的异常积累和过度稳定，从而为Abeta低聚物诱导的早期突触衰竭提供了机制和分子基础。

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