title: Pseudocatalytic Antiaggregation Activity of Antibodies: Immunoglobulins can Influence α-Synuclein Aggregation at Substoichiometric Concentrations.
abstract: Protein aggregation is involved in a variety of diseases. Alteration of the aggregation pathway, either to produce less toxic structures or to increase aggregate clearance, is a promising therapeutic route. Both active and passive immunization has been used for this purpose. However, the mechanism of action of antibodies on protein aggregates is not completely clear especially given poor ability of antibodies to cross blood-brain barrier. Here, we have shown that antibodies can interfere with protein aggregation at substoichiometric concentrations (as low as 1:1000 antibody to protein ratio). This is an indication that antibodies interact with aggregation intermediates in chaperone-like manner altering the aggregation pathways at very low antibody levels. This observation supports earlier suggestions that antibodies can inhibit aggregation by interaction with low abundance aggregation intermediates.
authors.affiliation: Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, 33612, USA.|Byrd Alzheimer Institute, Morsani College of Medicine, University of South Florida, Tampa, FL, 33612, USA.
authors.forename: Leonid
authors.initials: L
authors.lastname: Breydo
authors.affiliation: Byrd Alzheimer Institute, Morsani College of Medicine, University of South Florida, Tampa, FL, 33612, USA.|Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL, 33612, USA.
authors.forename: Dave
authors.initials: D
authors.lastname: Morgan
authors.affiliation: Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, 33612, USA. vuversky@health.usf.edu.|Byrd Alzheimer Institute, Morsani College of Medicine, University of South Florida, Tampa, FL, 33612, USA. vuversky@health.usf.edu.|Department of Biological Sciences, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah, 21589, Kingdom of Saudi Arabia. vuversky@health.usf.edu.|Institute for Biological Instrumentation, Russian Academy of Sciences, Pushchino, Moscow Region, Russian Federation, 142290. vuversky@health.usf.edu.|Laboratory of Structural Dynamics, Stability and Folding of Proteins, Institute of Cytology, Russian Academy of Sciences, St. Petersburg, Russian Federation. vuversky@health.usf.edu.
authors.forename: Vladimir N
authors.initials: VN
authors.lastname: Uversky
mesh_terms: D000906:Antibodies / Q000378:metabolism* / Q000494:pharmacology; D052160:Benzothiazoles; D055162:Biocatalysis; D001681:Biological Assay; D002942:Circular Dichroism; D005453:Fluorescence; D007700:Kinetics; D066329:Protein Aggregates / Q000187:drug effects; D066263:Protein Aggregation, Pathological; D013844:Thiazoles / Q000378:metabolism; D051844:alpha-Synuclein / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D000906:Antibodies; D052160:Benzothiazoles; D066329:Protein Aggregates; D013844:Thiazoles; D051844:alpha-Synuclein; C009462:thioflavin T
keywords: Antibodies; Parkinson’s disease; Protein aggregation; α-Synuclein
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