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阿尔茨海默病中高尔基体组织的改变:原因还是结果?

Alterations of Golgi organization in Alzheimer's disease: A cause or a consequence?

作者信息

Ayala Inmaculada, Colanzi Antonino

机构信息

Institute of Protein Biochemistry, National Research Council, Via P. Castellino 111, 80131 Naples, Italy.

出版信息

Tissue Cell. 2017 Apr;49(2 Pt A):133-140. doi: 10.1016/j.tice.2016.11.007. Epub 2016 Nov 19.

Abstract

The Golgi apparatus is a central organelle of the secretory pathway involved in the post-translational modification and sorting of lipids and proteins. In mammalian cells, the Golgi apparatus is composed of stacks of cisternae organized in polarized manner, which are interconnected by membrane tubules to constitute the Golgi ribbon, located in the proximity of the centrosome. Besides the processing and transport of cargo, the Golgi complex is actively involved in the regulation of mitotic entry, cytoskeleton organization and dynamics, calcium homeostasis, and apoptosis, representing a signalling platform for the control of several cellular functions, including signalling initiated by receptors located at the plasma membrane. Alterations of the conventional Golgi organization are associated to many disorders, such as cancer or different neurodegenerative diseases. In this review, we examine the functional implications of modifications of Golgi structure in neurodegenerative disorders, with a focus on the role of Golgi fragmentation in the development of Alzheimer's disease. The comprehension of the mechanism that induces Golgi fragmentation and of its downstream effects on neuronal function have the potential to contribute to the development of more effective therapies to treat or prevent some of these disorders.

摘要

高尔基体是分泌途径的核心细胞器,参与脂质和蛋白质的翻译后修饰与分选。在哺乳动物细胞中,高尔基体由以极化方式排列的扁平囊堆叠组成,这些扁平囊通过膜性小管相互连接,构成位于中心体附近的高尔基体带。除了对货物进行加工和运输外,高尔基体复合体还积极参与有丝分裂进入、细胞骨架组织与动态变化、钙稳态以及细胞凋亡的调控,代表了一个控制多种细胞功能的信号平台,包括由位于质膜上的受体引发的信号传导。传统高尔基体组织的改变与许多疾病相关,如癌症或不同的神经退行性疾病。在本综述中,我们研究了高尔基体结构改变在神经退行性疾病中的功能意义,重点关注高尔基体碎片化在阿尔茨海默病发展中的作用。理解诱导高尔基体碎片化的机制及其对神经元功能的下游影响,有可能有助于开发更有效的疗法来治疗或预防其中一些疾病。

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