title: Correlation between protective immunity to α-synuclein aggregates, oxidative stress and inflammation.
abstract: OBJECTIVE
  Protein aggregation leading to central amyloid deposition is implicated in Parkinson's disease (PD). During disease progression, inflammation and oxidative stress may well invoke humoral immunity against pathological aggregates of PD-associated α-synuclein. The aim was to investigate any possible concurrence between autoimmune responses to α-synuclein monomers, oligomers or fibrils with oxidative stress and inflammation.
  
  
  METHODS
  The formation of α-synuclein amyloid species was assessed by thioflavin-T assay and atomic force microscopy was employed to confirm their morphology. Serum autoantibody titers to α-synuclein conformations were determined by ELISA. Enzyme activity and concentrations of oxidative stress/inflammatory indicators were evaluated by enzyme and ELISA protocols.
  
  
  RESULTS
  In PD patient sera, a differential increase in autoantibody titers to α-synuclein monomers, toxic oligomers or fibrils was associated with boosted levels of the pro-inflammatory cytokine interleukin-6 and tumour necrosis factor-α, but a decrease in interferon-γ concentration. In addition, levels of malondialdehyde were elevated whilst those of glutathione were reduced along with decrements in the activity of the antioxidants: superoxide dismutase, catalase and glutathione transferase.
  
  
  CONCLUSIONS
  It is hypothesized that the generation of α-synuclein amyloid aggregates allied with oxidative stress and inflammatory reactions may invoke humoral immunity protecting against dopaminergic neuronal death. Hence, humoral immunity is a common integrative factor throughout PD progression which is directed towards prevention of further neurodegeneration, so potential treatment strategies should attempt to maintain PD patient immune status.
authors.forename: Marina A
authors.initials: MA
authors.lastname: Gruden
authors.forename: Kiran
authors.initials: K
authors.lastname: Yanamandra
authors.forename: Valery G
authors.initials: VG
authors.lastname: Kucheryanu
authors.forename: Olga R
authors.initials: OR
authors.lastname: Bocharova
authors.forename: Vladimir V
authors.initials: VV
authors.lastname: Sherstnev
authors.forename: Ludmilla A
authors.initials: LA
authors.lastname: Morozova-Roche
authors.forename: Robert D E
authors.initials: RDE
authors.lastname: Sewell
mesh_terms: D000328:Adult; D000368:Aged; D000682:Amyloid / Q000009:adverse effects / Q000276:immunology / Q000378:metabolism; D001323:Autoantibodies / Q000096:biosynthesis* / Q000097:blood / Q000627:therapeutic use; D005260:Female; D006801:Humans; D056724:Immunity, Humoral / Q000276:immunology; D007249:Inflammation / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D018836:Inflammation Mediators / Q000097:blood / Q000276:immunology / Q000378:metabolism; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000627:therapeutic use; D015850:Interleukin-6 / Q000096:biosynthesis / Q000097:blood / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000276:immunology*; D010300:Parkinson Disease / Q000276:immunology* / Q000473:pathology* / Q000517:prevention & control; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000097:blood / Q000627:therapeutic use; D051844:alpha-Synuclein / Q000276:immunology* / Q000378:metabolism
chemical_list: D000682:Amyloid; D001323:Autoantibodies; C508600:IL6 protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D051844:alpha-Synuclein; D007371:Interferon-gamma