Pieri Laura, Chafey Philippe, Le Gall Morgane, Clary Guilhem, Melki Ronald, Redeker Virginie
Paris-Saclay Institute of Neuroscience, CNRS, Université Paris-Saclay, Avenue de la terrasse, 91190 Gif-sur-Yvette, France.
Plate-forme protéomique 3P5, Université Paris Descartes, Sorbonne Paris Cité, France; Inserm U1016, Institut Cochin, Paris, France; CNRS, UMR8104, Paris, France.
Biochim Biophys Acta. 2016 Jan;1860(1 Pt A):8-19. doi: 10.1016/j.bbagen.2015.10.007. Epub 2015 Oct 22.
α-Synuclein (α-Syn) fibrils are the main constituent of Lewy bodies and a neuropathological hallmark of Parkinson's disease (PD). The propagation of α-Syn assemblies from cell to cell suggests that they are involved in PD progression. We previously showed that α-Syn fibrils are toxic because of their ability to bind and permeabilize cell membranes. Here, we document the cellular response in terms of proteome changes of SH-SY5Y cells exposed to exogenous α-Syn fibrils.
We compare the proteomes of cells of neuronal origin exposed or not either to oligomeric or fibrillar α-Syn using two dimensional differential in-gel electrophoresis (2D-DIGE) and mass spectrometry.
Only α-Syn fibrils induce significant changes in the proteome of SH-SY5Y cells. In addition to proteins associated to apoptosis and toxicity, or proteins previously linked to neurodegenerative diseases, we report an overexpression of proteins involved in intracellular vesicle trafficking. We also report a remarkable increase in fibrillar α-Syn heterogeneity, mainly due to C-terminal truncations.
Our results show that cells of neuronal origin adapt their proteome to exogenous α-Syn fibrils and actively modify those assemblies.
Cells of neuronal origin adapt their proteome to exogenous toxic α-Syn fibrils and actively modify those assemblies. Our results bring insights into the cellular response and clearance events the cells implement to face the propagation of α-Syn assemblies associated to pathology.
α-突触核蛋白（α-Syn）纤维是路易小体的主要成分，也是帕金森病（PD）的神经病理学标志。α-Syn聚集体在细胞间的传播表明它们参与了PD的进展。我们之前表明，α-Syn纤维具有毒性，因为它们能够结合并使细胞膜通透。在此，我们记录了暴露于外源性α-Syn纤维的SH-SY5Y细胞蛋白质组变化方面的细胞反应。
我们使用二维差异凝胶电泳（2D-DIGE）和质谱法比较了暴露或未暴露于寡聚体或纤维状α-Syn的神经元源性细胞的蛋白质组。
只有α-Syn纤维会诱导SH-SY5Y细胞蛋白质组发生显著变化。除了与凋亡和毒性相关的蛋白质，或先前与神经退行性疾病相关的蛋白质外，我们还报告了参与细胞内囊泡运输的蛋白质的过表达。我们还报告了纤维状α-Syn异质性的显著增加，主要是由于C末端截短。
我们的结果表明，神经元源性细胞会使其蛋白质组适应外源性α-Syn纤维，并积极修饰这些聚集体。
神经元源性细胞会使其蛋白质组适应外源性有毒α-Syn纤维，并积极修饰这些聚集体。我们的结果为细胞面对与病理学相关的α-Syn聚集体传播时实施的细胞反应和清除事件提供了见解。
