title: Cellular response of human neuroblastoma cells to α-synuclein fibrils, the main constituent of Lewy bodies.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Our results show that cells of neuronal origin adapt their proteome to exogenous α-Syn fibrils and actively modify those assemblies.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Paris-Saclay Institute of Neuroscience, CNRS, Université Paris-Saclay, Avenue de la terrasse, 91190 Gif-sur-Yvette, France.
authors.forename: Laura
authors.initials: L
authors.lastname: Pieri
authors.affiliation: Plate-forme protéomique 3P5, Université Paris Descartes, Sorbonne Paris Cité, France; Inserm U1016, Institut Cochin, Paris, France; CNRS, UMR8104, Paris, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Chafey
authors.affiliation: Plate-forme protéomique 3P5, Université Paris Descartes, Sorbonne Paris Cité, France; Inserm U1016, Institut Cochin, Paris, France; CNRS, UMR8104, Paris, France.
authors.forename: Morgane
authors.initials: M
authors.lastname: Le Gall
authors.affiliation: Plate-forme protéomique 3P5, Université Paris Descartes, Sorbonne Paris Cité, France; Inserm U1016, Institut Cochin, Paris, France; CNRS, UMR8104, Paris, France.
authors.forename: Guilhem
authors.initials: G
authors.lastname: Clary
authors.affiliation: Paris-Saclay Institute of Neuroscience, CNRS, Université Paris-Saclay, Avenue de la terrasse, 91190 Gif-sur-Yvette, France.
authors.forename: Ronald
authors.initials: R
authors.lastname: Melki
authors.affiliation: Paris-Saclay Institute of Neuroscience, CNRS, Université Paris-Saclay, Avenue de la terrasse, 91190 Gif-sur-Yvette, France. Electronic address: virginie.redeker@lebs.cnrs-gif.fr.
authors.forename: Virginie
authors.initials: V
authors.lastname: Redeker
mesh_terms: D045744:Cell Line, Tumor; D006801:Humans; D016631:Lewy Bodies / Q000737:chemistry*; D009447:Neuroblastoma / Q000473:pathology*; D011499:Protein Processing, Post-Translational; D020543:Proteome; D057825:Two-Dimensional Difference Gel Electrophoresis; D051844:alpha-Synuclein / Q000737:chemistry / Q000502:physiology*
chemical_list: D020543:Proteome; D051844:alpha-Synuclein
keywords: 2D-DIGE; Parkinson's Disease; Post-translational modifications; Proteomic; α-Synuclein