Abstract
Spreading of alpha-synuclein (alpha Syn) may play an important role in Parkinson's disease and related synucleinopathies. Passive immunization with anti-alpha Syn antibodies is a promising method to slow down the spreading process and thereby the progression of synucleinopathies. Currently, it remains elusive which specific characteristics are essential to render therapeutic antibodies efficacious. Here, we established a neuronal co-culture model, in which alpha Syn species are being released from alpha Syn-overexpressing cells and induce toxicity in a priori healthy GFP-expressing cells. In this model, we investigated the protective efficacy of three anti-alpha Syn antibodies. Only two of these antibodies, one C-terminal and one N-terminal, protected from alpha Syn-induced toxicity by inhibiting the uptake of spreading-competent alpha Syn from the cell culture medium. Neither the binding epitope nor the affinity of the antibodies towards recombinant alpha Syn could explain differences in biological efficacy. However, both protective antibodies formed more stable antibody-alpha Syn complexes than the non-protective antibody. These findings indicate that the stability of antibody-alpha Syn complexes may be more important to confer protection than the binding epitope or affinity to recombinant alpha Syn.
| Dokumententyp: | Zeitschriftenartikel |
|---|---|
| Fakultät: | Medizin |
| Themengebiete: | 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit |
| ISSN: | 0893-7648 |
| Sprache: | Englisch |
| Dokumenten ID: | 115357 |
| Datum der Veröffentlichung auf Open Access LMU: | 02. Apr. 2024, 08:13 |
| Letzte Änderungen: | 02. Apr. 2024, 08:13 |
| DFG: | Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198 |
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