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The release and transmission of amyloid precursor protein via exosomes
Neurochemistry international ( IF 4.4 ) Pub Date : 2017-12-23 , DOI: 10.1016/j.neuint.2017.12.009
Tingting Zheng , Xiaoqing Wu , Xiaojie Wei , Mingkai Wang , Baorong Zhang

Amyloid precursor protein (APP) processing is central in Alzheimer's disease (AD) pathogenesis. The healthy unaffected neurons suffer the transmission of amyloid protein from pathologically affected neurons, which may play an important role in the anatomical spread of the disease. Exosomes are appropriate candidates for transmission of amyloid species, because of their potential role as “intercellular transportation”. To address a role of secreted exosomes in neuronal homeostasis in AD, we harvested exosomes from the conditioned medium of HEK293-APP Swe/Ind cells. We have demonstrated that these exosomes contained APP and were capable of efficiently transferring APP to normal primary neurons. Moreover, these exosomes had dose-dependent detrimental effect on cultured neurons. Our results suggest a key mechanism underlying the spread of amyloid protein in the brain and the acceleration of pathology in AD; exosomes secretion serves to amplify and propagate Alzheimer's disease related pathology.



中文翻译:

淀粉样前体蛋白通过外泌体的释放和传播

淀粉样前体蛋白(APP)的加工在阿尔茨海默氏病(AD)发病机理中至关重要。健康的未受影响的神经元会从病理上受影响的神经元中传递淀粉样蛋白,这可能在疾病的解剖学传播中发挥重要作用。外来体是淀粉样物质传输的合适候选者,因为它们具有“细胞间运输”的潜在作用。为解决分泌的外泌体在AD神经元稳态中的作用,我们从HEK293-APP Swe / Ind细胞的条件培养基中收获了外泌体。我们已经证明这些外泌体包含APP,并且能够有效地将APP转移到正常的初级神经元。此外,这些外泌体对培养的神经元具有剂量依赖性的有害作用。我们的研究结果提示了淀粉样蛋白在大脑中扩散和AD病理加速的关键机制。外泌体分泌起放大和传播阿尔茨海默氏病相关病理的作用。

更新日期:2017-12-23
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