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Exp Neurobiol 2022; 31(1): 29-41
Published online February 28, 2022
© The Korean Society for Brain and Neural Sciences
Minsun Choi1†, Tae-kyung Kim1,3†, Jinhyung Ahn2, Jun Sung Lee1, Byung Chul Jung1, Sungwon An2, Dongin Kim2, Min Jae Lee4, Inhee Mook-Jung4, Sang Hoon Lee2 and Seung-Jae Lee1*
1Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, 2ABL Bio, Inc., Seongnam 13488, 3Department of Exercise Physiology and Sport Science Institute, Korea National Sport University, Seoul 05541, 4Department of Biochemistry and Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea
Correspondence to: *To whom correspondence should be addressed.
TEL: 82-2-3668-7037, FAX: 82-2-447-5683
†These authors contributed equally to this article.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abnormal aggregation of α-synuclein is a key element in the pathogenesis of several neurodegenerative diseases, including Parkinson’s disease (PD), dementia with Lewy bodies, and multiple system atrophy. α-synuclein aggregation spreads through various brain regions during the course of disease progression, a propagation that is thought to be mediated by the secretion and subsequent uptake of extracellular α-synuclein aggregates between neuronal cells. Thus, aggregated forms of this protein have emerged as promising targets for disease-modifying therapy for PD and related diseases. Here, we generated and characterized conformation-specific antibodies that preferentially recognize aggregated forms of α-synuclein. These antibodies promoted phagocytosis of extracellular α-synuclein aggregates by microglial cells and interfered with cell-to-cell propagation of α-synuclein. In an α-synuclein transgenic model, passive immunization with aggregate-specific antibodies significantly ameliorated pathological phenotypes, reducing α-synuclein aggregation, gliosis, inflammation, and neuronal loss. These results suggest that conformation-specific antibodies targeting α-synuclein aggregates are promising therapeutic agents for PD and related synucleinopathies.
Keywords: Parkinson’s disease, Immunotherapy, Synuclein, Microglia