| Autor: |
Tomasz Brudek, Kristian Winge, Jonas Folke, Søren Christensen, Karina Fog, Bente Pakkenberg, Lars Østergaard Pedersen |
| Jazyk: |
angličtina |
| Rok vydání: |
2017 |
| Předmět: |
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| Zdroj: |
Molecular Neurodegeneration, Vol 12, Iss 1, Pp 1-16 (2017) |
| Druh dokumentu: |
article |
| ISSN: |
1750-1326 |
| DOI: |
10.1186/s13024-017-0187-7 |
| Popis: |
Abstract Background Parkinson’s’ disease (PD) and Multiple System Atrophy (MSA) are progressive brain disorders characterized by intracellular accumulations of α-synuclein and nerve cell loss in specific brain areas. This loss causes problems with movement, balance and/or autonomic functions. Naturally occurring autoantibodies (NAbs) play potentially an important role in clearing or/and blocking circulating pathological proteins. Little is known about the functional properties of anti-α-synuclein NAbs in PD and MSA, and there have been opposing reports regarding their plasma concentrations in these disorders. Methods We have investigated the apparent affinity of anti-α-synuclein NAbs in plasma samples from 46 PD patients, 18 MSA patients and 41 controls using competitive enzyme-linked immunosorbent assay (ELISA) and Meso Scale Discovery (MSD) set-ups. Results We found that the occurrence of high affinity anti-α-synuclein NAbs in plasma from PD patients is reduced compared to healthy controls, and nearly absent in plasma from MSA patients. Also, levels of α-synuclein/NAbs immunocomplexes is substantially reduced in plasma from both patient groups. Further, cross binding of anti-α-synuclein NAbs with β- and γ-synuclein monomers suggest, the high affinity anti-α-synuclein plasma component, seen in healthy individuals, is directed mainly against C-terminal epitopes. Furthermore, we also observed reduced occurrence of high affinity anti-phosphorylated-α-synuclein NAbs in plasma from PD and MSA patients. Conclusions One interpretation implies that these patients may have impaired ability to clear and/or block the effects of pathological α-synuclein due to insufficient/absent concentration of NAbs and as such provides a rationale for testing immune-based therapeutic strategies directed against pathological α-synuclein. Following this interpretation, we can hypothesize that high affinity autoantibodies efficiently bind and clear potentially pathological species of α-synuclein in healthy brain, and that this mechanism is impaired or absent in PD and MSA patients. |
| Databáze: |
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| Externí odkaz: |
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