Pseudocatalytic Antiaggregation Activity of Antibodies: Immunoglobulins can Influence α-Synuclein Aggregation at Substoichiometric Concentrations

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• 作者：Leonid Breydo ; Dave Morgan ; Vladimir N. Uversky
• 关键词：Parkinson’s disease ; Antibodies ; Protein aggregation ; α ; Synuclein
• 刊名：Molecular Neurobiology
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：53
• 期：3
• 页码：1949-1958
• 全文大小：4,813 KB
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• 作者单位：Leonid Breydo (1) (2)
  Dave Morgan (2) (3)
  Vladimir N. Uversky (1) (2) (4) (5) (6)
  
  1. Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, 33612, USA
  2. Byrd Alzheimer Institute, Morsani College of Medicine, University of South Florida, Tampa, FL, 33612, USA
  3. Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL, 33612, USA
  4. Department of Biological Sciences, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah, 21589, Kingdom of Saudi Arabia
  5. Institute for Biological Instrumentation, Russian Academy of Sciences, Pushchino, Moscow Region, Russian Federation, 142290
  6. Laboratory of Structural Dynamics, Stability and Folding of Proteins, Institute of Cytology, Russian Academy of Sciences, St. Petersburg, Russian Federation
  
• 刊物主题：Neurosciences; Neurobiology; Cell Biology; Neurology;
• 出版者：Springer US
• ISSN：1559-1182

文摘

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.