Golgi fragmentation in Alzheimer's disease.
Golgi fragmentation in Alzheimer's disease.
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DOI：
10.3389/fnins.2015.00340
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发表时间：
2015
影响因子：
4.3
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Joshi G;Bekier ME 2nd;Wang Y
高尔基体是膜蛋白和分泌蛋白翻译后修饰、分类和运输的重要细胞器。高尔基体的正常功能需要形成其独特的脑池堆积形态。高尔基体结构在多种神经退行性疾病中被破坏，提示在神经退行性疾病中高尔基体缺陷的共同机制和贡献。最近对阿尔茨海默病(AD)的一项研究表明，高尔基体堆积蛋白GRASP65的磷酸化破坏了其在高尔基体结构形成中的功能，导致高尔基体碎裂。抑制GRASP65的磷酸化可以恢复Aβ诱导的高尔基体形态，并减少Aβ的产生。神经元高尔基体结构和功能的紊乱可能直接影响突触和树突完整性所必需的各种蛋白质的运输、加工和分类。因此，高尔基体缺陷可能最终促进AD的发展。在目前的综述中，我们着重于高尔基体形态受损的细胞影响及其与阿尔茨海默病发展的潜在关系。
The Golgi apparatus is an essential cellular organelle for post-translational modifications, sorting, and trafficking of membrane and secretory proteins. Proper functionality of the Golgi requires the formation of its unique cisternal-stacking morphology. The Golgi structure is disrupted in a variety of neurodegenerative diseases, suggesting a common mechanism and contribution of Golgi defects in neurodegenerative disorders. A recent study on Alzheimer's disease (AD) revealed that phosphorylation of the Golgi stacking protein GRASP65 disrupts its function in Golgi structure formation, resulting in Golgi fragmentation. Inhibiting GRASP65 phosphorylation restores the Golgi morphology from Aβ-induced fragmentation and reduces Aβ production. Perturbing Golgi structure and function in neurons may directly impact trafficking, processing, and sorting of a variety of proteins essential for synaptic and dendritic integrity. Therefore, Golgi defects may ultimately promote the development of AD. In the current review, we focus on the cellular impact of impaired Golgi morphology and its potential relationship to AD disease development.