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.
Keywords: aggregation; Parkinson’s disease; intravenous immunoglobulins (IVIG); naturally occurring antibodies; alpha-synuclein CLICK TO REVIEW