Suppr超能文献

成纤维细胞生长因子2通过外泌体Rab8b/Rab31影响帕金森病相关分子网络。

FGF2 Affects Parkinson's Disease-Associated Molecular Networks Through Exosomal Rab8b/Rab31.

作者信息

Kumar Rohit, Donakonda Sainitin, Müller Stephan A, Bötzel Kai, Höglinger Günter U, Koeglsperger Thomas

机构信息

German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.

Faculty of Medicine, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany.

出版信息

Front Genet. 2020 Sep 25;11:572058. doi: 10.3389/fgene.2020.572058. eCollection 2020.

Abstract

Ras-associated binding (Rab) proteins are small GTPases that regulate the trafficking of membrane components during endocytosis and exocytosis including the release of extracellular vesicles (EVs). Parkinson's disease (PD) is one of the most prevalent neurodegenerative disorder in the elderly population, where pathological proteins such as alpha-synuclein (α-Syn) are transmitted in EVs from one neuron to another neuron and ultimately across brain regions, thereby facilitating the spreading of pathology. We recently demonstrated fibroblast growth factor-2 (FGF2) to enhance the release of EVs and delineated the proteomic signature of FGF2-triggered EVs in cultured primary hippocampal neurons. Out of 235 significantly upregulated proteins, we found that FGF2 specifically enriched EVs for the two Rab family members and . Consequently, we investigated the interactions of and using a network analysis approach in order to estimate the global influence of their enrichment in EVs. To achieve this, we have demarcated a protein-protein interaction network (PPiN) for these Rabs and identified the proteins associated with PD in various cellular components of the central nervous system (CNS), in different brain regions, and in the enteric nervous system (ENS). A total of 126 direct or indirect interactions were reported for two Rab candidates, out of which 114 are interactions and 54 are interactions, ultimately resulting in an individual interaction score (IS) of 90.48 and 42.86%, respectively. Conclusively, these results for the first time demonstrate the relevance of FGF2-induced Rab-enrichment in EVs and its potential to regulate PD pathophysiology.

摘要

Ras相关结合(Rab)蛋白是一类小GTP酶,在胞吞作用和胞吐作用(包括细胞外囊泡(EV)的释放)过程中调节膜成分的运输。帕金森病(PD)是老年人群中最常见的神经退行性疾病之一,其中病理性蛋白质如α-突触核蛋白(α-Syn)通过EV从一个神经元传递到另一个神经元,并最终跨越脑区,从而促进病理状态的传播。我们最近证明成纤维细胞生长因子2(FGF2)可增强EV的释放,并描绘了培养的原代海马神经元中FGF2触发的EV的蛋白质组特征。在235种显著上调的蛋白质中,我们发现FGF2特异性地富集了两种Rab家族成员的EV。因此,我们使用网络分析方法研究了这两种Rab的相互作用,以评估它们在EV中富集的全局影响。为了实现这一点,我们为这些Rab划定了一个蛋白质-蛋白质相互作用网络(PPiN),并确定了在中枢神经系统(CNS)的各种细胞成分、不同脑区和肠神经系统(ENS)中与PD相关的蛋白质。两种Rab候选物共报告了126种直接或间接相互作用,其中114种是与某种Rab的相互作用,54种是与另一种Rab的相互作用,最终分别产生了90.48和42.86%的个体相互作用得分(IS)。总之,这些结果首次证明了FGF2诱导的Rab在EV中的富集及其调节PD病理生理学的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb94/7545478/a7b682cb0a96/fgene-11-572058-g001.jpg

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验