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Correlation between Protective Immunity to alpha-Synuclein Aggregates, Oxidative Stress and Inflammation
Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
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2012 (English)In: Neuroimmunomodulation, ISSN 1021-7401, E-ISSN 1423-0216, Vol. 19, no 6, 334-342 p.Article in journal (Refereed) Published
Abstract [en]

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 alpha-synuclein. The aim was to investigate any possible concurrence between autoimnnune responses to alpha-synuclein monomers, oligomers or fibrils with oxidative stress and inflammation.

Methods: The formation of alpha-synuclein amyloid species was assessed by thioflavin-T assay and atomic force microscopy was employed to confirm their morphology. Serum autoantibody titers to alpha-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 alpha-synuclein monomers, toxic oligomers or fibrils was associated with boosted levels of the pro-inflammatory cytokine interleukin-6 and tumour necrosis factor-alpha, but a decrease in interferon-gamma 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 alpha-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. Copyright (c) 2012 S. Karger AG, Basel

Place, publisher, year, edition, pages
2012. Vol. 19, no 6, 334-342 p.
Keyword [en]
Parkinson's disease, alpha-Synuclein oligonners, Autoantibodies, Cytokines, Oxidative stress
National Category
Immunology in the medical area Endocrinology and Diabetes Neurosciences Neurology
URN: urn:nbn:se:umu:diva-62178DOI: 10.1159/000341400ISI: 000310764400002OAI: diva2:575462
Available from: 2012-12-10 Created: 2012-12-10 Last updated: 2012-12-10Bibliographically approved

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Yanamandra, KiranMorozova-Roche, Ludmilla A.
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