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Molecular Neurobiology

, Volume 53, Issue 3, pp 1949–1958 | Cite as

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

  • Leonid Breydo
  • Dave Morgan
  • Vladimir N. UverskyEmail author
Article

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.

Keywords

Parkinson’s disease Antibodies Protein aggregation α-Synuclein 

Notes

Acknowledgments

This work was supported by the USF Health Byrd Alzheimer's Institute. DGM is supported by NIH NS76308.

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Leonid Breydo
    • 1
    • 2
  • Dave Morgan
    • 2
    • 3
  • Vladimir N. Uversky
    • 1
    • 2
    • 4
    • 5
    • 6
    Email author
  1. 1.Department of Molecular MedicineMorsani College of Medicine, University of South FloridaTampaUSA
  2. 2.Byrd Alzheimer InstituteMorsani College of Medicine, University of South FloridaTampaUSA
  3. 3.Department of Molecular Pharmacology and Physiology, Morsani College of MedicineUniversity of South FloridaTampaUSA
  4. 4.Department of Biological Sciences, Faculty of ScienceKing Abdulaziz UniversityJeddahKingdom of Saudi Arabia
  5. 5.Institute for Biological InstrumentationRussian Academy of SciencesPushchinoRussian Federation
  6. 6.Laboratory of Structural Dynamics, Stability and Folding of Proteins, Institute of CytologyRussian Academy of SciencesSt. PetersburgRussian Federation

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