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α-Synuclein Trafficking in Parkinson's Disease: Insights From Fly and Mouse Models.
ASN Neuro ( IF 4.7 ) Pub Date : 2018-11-30 , DOI: 10.1177/1759091418812587
Jingjing Cheng 1, 2 , Qingqing Lu 2, 3 , Li Song 3 , Margaret S Ho 1
Affiliation  

Protein aggregation and accumulation are common pathological hallmarks in neurodegenerative diseases. To efficiently clear and eliminate such aggregation becomes an important cellular strategy for cell survival. Lewy bodies inclusion and aggregation of α-Synuclein (α-Syn) during the pathogenesis of Parkinson's disease (PD) serve as a good example and are potentially linked to other pathological PD features such as progressive dopaminergic neuron cell death, behavioral defects, and nonmotor symptoms like anosmia, cognitive impairment, and depression. Years of research have revealed a variety of mechanisms underlying α-Syn aggregation, clearance, and spread. Particularly, vesicular routes associated with the trafficking of α-Syn, leading to its aggregation and accumulation, have been shown to play vital roles in PD pathogenesis. How α-Syn proteins propagate among cells in a prion-like manner, either from or to neurons and glia, via means of uptake or secretion, are questions under active investigation and have been of central interest in the field of PD study. This review covers components and pathways of possible vesicular routes involved in α-Syn trafficking. Events including but not limited to exocytosis and endocytosis will be discussed within the context of an overall cellular trafficking theme. Recent advances on α-Syn trafficking mechanisms and their significance in mediating PD pathogenesis will be thoroughly reviewed, ending with a discussion on the advantages and limitations of different animal PD models.

中文翻译:

帕金森氏病中的α-突触核蛋白贩运:蝇和小鼠模型的见解。

蛋白质的聚集和积累是神经退行性疾病中常见的病理标志。有效清除和消除这种聚集成为细胞存活的重要细胞策略。帕金森氏病(PD)发病过程中的路易体α-突触核蛋白(α-Syn)的包合和聚集是一个很好的例子,并可能与其他病理性PD特征相关,例如进行性多巴胺能神经元细胞死亡,行为缺陷和非运动性失眠,认知障碍和抑郁等症状。多年的研究揭示了各种α-Syn聚集,清除和扩散的机制。特别地,已经证明与α-Syn的运输相关的囊泡途径导致其聚集和积累在PD发病机理中起着至关重要的作用。α-Syn蛋白如何通过摄取或分泌的方式,以like病毒样的方式在细胞之间,从神经元和神经胶质或向神经元和神经胶质的细胞传播,是正在积极研究的问题,并且在PD研究领域已引起人们的广泛关注。这项审查涵盖了α-Syn贩运中可能的囊泡途径的组成部分和途径。包括但不限于胞吐作用和胞吞作用的事件将在总体细胞贩运主题的背景下进行讨论。本文将对α-Syn转运机制的最新进展及其在介导PD发病机理中的意义进行全面回顾,最后讨论不同动物PD模型的优势和局限性。是正在积极研究中的问题,并且在PD研究领域中引起了人们的关注。这项审查涵盖了α-Syn贩运中可能的囊泡途径的组成部分和途径。包括但不限于胞吐作用和胞吞作用的事件将在总体细胞贩运主题的背景下进行讨论。本文将对α-Syn转运机制的最新进展及其在介导PD发病机理中的意义进行全面回顾,最后讨论不同动物PD模型的优势和局限性。是正在积极研究中的问题,并且在PD研究领域中引起了人们的关注。这项审查涵盖了α-Syn贩运中可能的囊泡途径的组成部分和途径。包括但不限于胞吐作用和胞吞作用的事件将在总体细胞贩运主题的背景下进行讨论。本文将对α-Syn转运机制的最新进展及其在介导PD发病机理中的意义进行全面回顾,最后讨论不同动物PD模型的优势和局限性。包括但不限于胞吐作用和胞吞作用的事件将在总体细胞贩运主题的背景下进行讨论。本文将对α-Syn转运机制的最新进展及其在介导PD发病机理中的意义进行全面回顾,最后讨论不同动物PD模型的优势和局限性。包括但不限于胞吐作用和胞吞作用的事件将在总体细胞贩运主题的背景下进行讨论。本文将对α-Syn转运机制的最新进展及其在介导PD发病机理中的意义进行全面回顾,最后讨论不同动物PD模型的优势和局限性。
更新日期:2019-11-01
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