학술논문
Binding Stability of Antibody-α-Synuclein Complexes Predicts the Protective Efficacy of Anti-α-synuclein Antibodies.
Document Type
Academic Journal
Author
Höllerhage M; Department of Neurology, Hannover Medical School, Hannover, D-30625, Germany. hoellerhage.matthias@mh-hannover.de.; Wolff A; Department of Neurology, Technical University of Munich (TUM), D-81675, Munich, Germany.; Chakroun T; Department of Neurology, Technical University of Munich (TUM), D-81675, Munich, Germany.; Department of Translational Neurodegeneration, German Center for Neurodegenerative Diseases (DZNE), D-81377, Munich, Germany.; Evsyukov V; Department of Neurology, Hannover Medical School, Hannover, D-30625, Germany.; Duan L; Department of Neurology, Hannover Medical School, Hannover, D-30625, Germany.; Chua OW; Department of Neurology, Hannover Medical School, Hannover, D-30625, Germany.; Tang Q; Department of Translational Neurodegeneration, German Center for Neurodegenerative Diseases (DZNE), D-81377, Munich, Germany.; Koeglsperger T; Department of Translational Neurodegeneration, German Center for Neurodegenerative Diseases (DZNE), D-81377, Munich, Germany.; Department of Neurology, Ludwig Maximilian University Munich, D-81377, Munich, Germany.; Höglinger GU; Department of Neurology, Hannover Medical School, Hannover, D-30625, Germany.; Department of Translational Neurodegeneration, German Center for Neurodegenerative Diseases (DZNE), D-81377, Munich, Germany.
Source
Publisher: Humana Press Country of Publication: United States NLM ID: 8900963 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1559-1182 (Electronic) Linking ISSN: 08937648 NLM ISO Abbreviation: Mol Neurobiol Subsets: MEDLINE
Subject
Language
English
Abstract
Spreading of alpha-synuclein (αSyn) may play an important role in Parkinson's disease and related synucleinopathies. Passive immunization with anti-αSyn 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 αSyn species are being released from αSyn-overexpressing cells and induce toxicity in a priori healthy GFP-expressing cells. In this model, we investigated the protective efficacy of three anti-αSyn antibodies. Only two of these antibodies, one C-terminal and one N-terminal, protected from αSyn-induced toxicity by inhibiting the uptake of spreading-competent αSyn from the cell culture medium. Neither the binding epitope nor the affinity of the antibodies towards recombinant αSyn could explain differences in biological efficacy. However, both protective antibodies formed more stable antibody-αSyn complexes than the non-protective antibody. These findings indicate that the stability of antibody-αSyn complexes may be more important to confer protection than the binding epitope or affinity to recombinant αSyn.
(© 2022. The Author(s).)
(© 2022. The Author(s).)