Trafficking of Muscarinic 1 Acetylcholine Receptor Regulated by VPS35 in Alzheimer's Disease.

IF 1.9 Current Alzheimer research Pub Date : 2024-01-01 DOI:10.2174/0115672050356990250111200217

Chen Wang, Xi Chen, Zhenzhen Yu

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Abstract

Introduction: Muscarinic 1 acetylcholine receptor (M1AChR) is a member of the Gprotein- coupled receptor superfamily, with the dysfunction being linked to the onset of Alzheimer's Disease (AD).

Aims: Retromer complex with Vacuolar Protein Sorting-35 (VPS35) as the core plays an important role in the transport of biological proteins and has been confirmed to be closely related to the pathogenesis of AD. This study was designed to determine whether VPS35 could affect the trafficking mechanism of M1AChRs.

Methods: The interaction between VPS35 and M1AChR was studied by co-immunoprecipitation method, and the recycling of M1AChR influence by VPS35 was analyzed using biotinylation technology.

Results: It was found that VPS35 affected the localization of M1AChR on the cell membrane by regulating intracellular M1AChR transport, thus controlling the M1AChR-mediated cholinergic signaling pathway.

Conclusion: The findings presented here provide a potential pathogenesis and pathway for the treatment of AD.

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VPS35调控毒蕈碱1乙酰胆碱受体在阿尔茨海默病中的转运

毒蕈碱1乙酰胆碱受体（M1AChR）是g蛋白偶联受体超家族的成员，其功能障碍与阿尔茨海默病（AD）的发病有关。目的：以液泡蛋白分选-35 （VPS35）为核心的逆转录复合物在生物蛋白的转运中起着重要作用，已被证实与AD的发病密切相关。本研究旨在确定VPS35是否会影响m1achr的转运机制。方法：采用共免疫沉淀法研究VPS35与M1AChR的相互作用，采用生物素化技术分析VPS35对M1AChR回收的影响。结果：发现VPS35通过调节细胞内M1AChR转运影响M1AChR在细胞膜上的定位，从而控制M1AChR介导的胆碱能信号通路。结论：本研究结果为AD的治疗提供了一种潜在的发病机制和途径。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Current Alzheimer research

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