Amyloid β production along the neuronal secretory pathway: Dangerous liaisons in the Golgi?,Traffic

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Amyloid β production along the neuronal secretory pathway: Dangerous liaisons in the Golgi?
Traffic ( IF 3.6 ) Pub Date : 2021-06-29 , DOI: 10.1111/tra.12808
Lou Fourriere ₁ , Paul A Gleeson ₁

Affiliation

β-amyloid peptides (Aβ) are generated in intracellular compartments of neurons and secreted to form cytotoxic fibrils and plaques. Dysfunctional membrane trafficking contributes to aberrant Aβ production and Alzheimer's disease. Endosomes represent one of the major sites for Aβ production and recently the Golgi has re-emerged also as a major location for amyloid precursor protein (APP) processing and Aβ production. Based on recent findings, here we propose that APP processing in the Golgi is finely tuned by segregating newly-synthesised APP and the β-secretase BACE1 within the Golgi and into distinct trans-Golgi network transport pathways. We hypothesise that there are multiple mechanisms responsible for segregating APP and BACE1 during transit through the Golgi, and that perturbation in Golgi morphology associated with Alzheimer's disease, and or changes in cholesterol metabolism associated with Alzheimer's disease risk factors, may lead to a loss of partitioning and enhanced Aβ production.

中文翻译：

沿着神经元分泌途径产生淀粉样蛋白 β：高尔基体中的危险联络人？

β-淀粉样肽 (Aβ) 在神经元的细胞内隔室中产生并分泌以形成细胞毒性原纤维和斑块。功能失调的膜运输导致异常的 Aβ 产生和阿尔茨海默病。内体是 Aβ 产生的主要场所之一，最近高尔基体也重新出现，成为淀粉样前体蛋白 (APP) 加工和 Aβ 产生的主要场所。基于最近的研究结果，我们提出通过将新合成的 APP 和高尔基体内的 β-分泌酶 BACE1 分离成不同的反式来微调高尔基体中的 APP 加工。-高尔基网络运输路径。我们假设有多种机制负责在通过高尔基体的过程中分离 APP 和 BACE1，并且与阿尔茨海默病相关的高尔基体形态的扰动，和/或与阿尔茨海默病风险因素相关的胆固醇代谢的变化，可能导致分配的丧失并增强 Aβ 的产生。

更新日期：2021-08-20

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