This title appears in the Scientific Report :
2022
Please use the identifier:
http://dx.doi.org/10.3390/biom12030469 in citations.
Please use the identifier: http://hdl.handle.net/2128/31018 in citations.
Alpha-Synuclein-Specific Naturally Occurring Antibodies Inhibit Aggregation In Vitro and In Vivo
Alpha-Synuclein-Specific Naturally Occurring Antibodies Inhibit Aggregation In Vitro and In Vivo
Parkinson’s disease (PD) is associated with motor and non-motor symptoms and characterized by aggregates of alpha-synuclein (αSyn). Naturally occurring antibodies (nAbs) are part of the innate immune system, produced without prior contact to their specific antigen, and polyreactive. The abundance of...
Saved in:
Personal Name(s): | Braczynski, Anne K. |
---|---|
Sevenich, Marc / Gering, Ian / Kupreichyk, Tatsiana / Agerschou, Emil D. / Kronimus, Yannick / Habib, Pardes / Stoldt, Matthias / Willbold, Dieter / Schulz, Jörg B. / Bach, Jan-Philipp / Falkenburger, Björn H. / Hoyer, Wolfgang (Corresponding author) | |
Contributing Institute: |
Strukturbiochemie; IBI-7 Jara-Institut Quantum Information; INM-11 |
Published in: | Biomolecules, 12 (2022) 3, S. 469 - |
Imprint: |
Basel
MDPI
2022
|
PubMed ID: |
35327661 |
DOI: |
10.3390/biom12030469 |
Document Type: |
Journal Article |
Research Program: |
Information Processing in Neuronal Networks |
Link: |
OpenAccess |
Publikationsportal JuSER |
Please use the identifier: http://hdl.handle.net/2128/31018 in citations.
Parkinson’s disease (PD) is associated with motor and non-motor symptoms and characterized by aggregates of alpha-synuclein (αSyn). Naturally occurring antibodies (nAbs) are part of the innate immune system, produced without prior contact to their specific antigen, and polyreactive. The abundance of nAbs against αSyn is altered in patients with PD. In this work, we biophysically characterized nAbs against αSyn (nAbs-αSyn) and determined their biological effects. nAbs-αSyn were isolated from commercial intravenous immunoglobulins using column affinity purification. Biophysical properties were characterized using a battery of established in vitro assays. Biological effects were characterized in HEK293T cells transiently transfected with fluorescently tagged αSyn. Specific binding of nAbs-αSyn to monomeric αSyn was demonstrated by Dot blot, ELISA, and Surface Plasmon Resonance. nAbs-αSyn did not affect viability of HEK293T cells as reported by Cell Titer Blue and LDH Assays. nAbs-αSyn inhibited fibrillation of αSyn reported by the Thioflavin T aggregation assay. Altered fibril formation was confirmed with atomic force microscopy. In cells transfected with EGFP-tagged αSyn we observed reduced formation of aggresomes, perinuclear accumulations of αSyn aggregates. The results demonstrate that serum of healthy individuals contains nAbs that specifically bind αSyn and inhibit aggregation of αSyn in vitro. The addition of nAbs-αSyn to cultured cells affects intracellular αSyn aggregates. These findings help understanding the role of the innate immune systems for the pathogenesis of PD and suggest that systemic αSyn binding agents could potentially affect neuronal αSyn pathology. |