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

Current Alzheimer research Pub Date : 2025-01-28 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.

Method: 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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