Breydo Leonid, Morgan Dave, Uversky Vladimir N
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.
Mol Neurobiol. 2016 Apr;53(3):1949-1958. doi: 10.1007/s12035-015-9148-8. Epub 2015 Apr 2.
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.
蛋白质聚集与多种疾病相关。改变聚集途径，无论是产生毒性较小的结构还是增加聚集体清除率，都是一条有前景的治疗途径。主动免疫和被动免疫都已用于此目的。然而，抗体对蛋白质聚集体的作用机制尚不完全清楚，尤其是考虑到抗体穿越血脑屏障的能力较差。在此，我们表明抗体能够以亚化学计量浓度（低至抗体与蛋白质比例为1:1000）干扰蛋白质聚集。这表明抗体以类似伴侣蛋白的方式与聚集中间体相互作用，在极低抗体水平下改变聚集途径。这一观察结果支持了早期的观点，即抗体可通过与低丰度聚集中间体相互作用来抑制聚集。
