TY  - JOUR
AU  - Braczynski, Anne K.
AU  - Sevenich, Marc
AU  - Gering, Ian
AU  - Kupreichyk, Tatsiana
AU  - Agerschou, Emil D.
AU  - Kronimus, Yannick
AU  - Habib, Pardes
AU  - Stoldt, Matthias
AU  - Willbold, Dieter
AU  - Schulz, Jörg B.
AU  - Bach, Jan-Philipp
AU  - Falkenburger, Björn H.
AU  - Hoyer, Wolfgang
TI  - Alpha-Synuclein-Specific Naturally Occurring Antibodies Inhibit Aggregation In Vitro and In Vivo
JO  - Biomolecules
VL  - 12
IS  - 3
SN  - 2218-273X
CY  - Basel
PB  - MDPI
M1  - FZJ-2022-01728
SP  - 469 -
PY  - 2022
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:35327661
UR  - <Go to ISI:>//WOS:000775905700001
DO  - DOI:10.3390/biom12030469
UR  - https://juser.fz-juelich.de/record/906834
ER  -