α-突触核蛋白的细胞间传递

IF 3.5 3区医学 Q2 NEUROSCIENCES

Frontiers in Molecular Neuroscience Pub Date : 2024-09-11 DOI:10.3389/fnmol.2024.1470171

Shenjie Wu, Randy W. Schekman

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引用次数: 0

摘要

帕金森病（PD）的一个新主题是α-突触核蛋白病理学随着病情发展而扩散。在动物模型中注射预成形的α-突触核蛋白纤维（PFFs）的研究再现了帕金森病患者的病理扩散。在细胞和分子水平上，这种细胞间扩散需要α-突触核蛋白穿过各种膜屏障。最近的研究发现了促进这些过程的亚细胞器和蛋白质机制。在这篇综述中，我们讨论了α-突触核蛋白细胞间传输的拟议途径，包括非常规分泌、受体介导的摄取、内质体逃逸和纳米管介导的转移。此外，我们主张严格审查α-突触核蛋白在细胞外囊泡中定位的证据。

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Intercellular transmission of alpha-synuclein

An emerging theme in Parkinson’s disease (PD) is the propagation of α-synuclein pathology as the disease progresses. Research involving the injection of preformed α-synuclein fibrils (PFFs) in animal models has recapitulated the pathological spread observed in PD patients. At the cellular and molecular levels, this intercellular spread requires the translocation of α-synuclein across various membrane barriers. Recent studies have identified subcellular organelles and protein machineries that facilitate these processes. In this review, we discuss the proposed pathways for α-synuclein intercellular transmission, including unconventional secretion, receptor-mediated uptake, endosome escape and nanotube-mediated transfer. In addition, we advocate for a rigorous examination of the evidence for the localization of α-synuclein in extracellular vesicles.

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来源期刊

Frontiers in Molecular Neuroscience NEUROSCIENCES-

CiteScore

5.70

自引率

2.10%

发文量

669

审稿时长

14 weeks

期刊介绍： Frontiers in Molecular Neuroscience is a first-tier electronic journal devoted to identifying key molecules, as well as their functions and interactions, that underlie the structure, design and function of the brain across all levels. The scope of our journal encompasses synaptic and cellular proteins, coding and non-coding RNA, and molecular mechanisms regulating cellular and dendritic RNA translation. In recent years, a plethora of new cellular and synaptic players have been identified from reduced systems, such as neuronal cultures, but the relevance of these molecules in terms of cellular and synaptic function and plasticity in the living brain and its circuits has not been validated. The effects of spine growth and density observed using gene products identified from in vitro work are frequently not reproduced in vivo. Our journal is particularly interested in studies on genetically engineered model organisms (C. elegans, Drosophila, mouse), in which alterations in key molecules underlying cellular and synaptic function and plasticity produce defined anatomical, physiological and behavioral changes. In the mouse, genetic alterations limited to particular neural circuits (olfactory bulb, motor cortex, cortical layers, hippocampal subfields, cerebellum), preferably regulated in time and on demand, are of special interest, as they sidestep potential compensatory developmental effects.