The binding of monomeric amyloid ß peptide to serum albumin is affected by major plasma unsaturated fatty acids.

Human serum albumin (HSA) serves as a natural depot of amyloid ß peptide (Aß). Improvement of Aß binding to HSA should impede Alzheimer's disease (AD). We developed a method for quantitation of the interaction between monomeric Aß40/42 and HSA using surface plasmon resonance spectroscopy. The dissociation constant of HSA complex with recombinant Aß40/42 is 0.2-0.3 µM. Flemish variant of Aß40 has 2.5-10-fold higher affinity to HSA. The parameters of the HSA-Aß interaction are selectively sensitive to HSA binding of major plasma unsaturated fatty acids and Cu2+. Linoleic and arachidonic acids promote the HSA-Aß42 interaction. The developed methodology for quantitation of HSA-Aß interaction may serve as a tool for search of compounds favoring HSA-Aß interaction, thereby preventing AD progression.

Studies of the Process of Amyloid Formation by Aß Peptide.

Studies of the process of amyloid formation by Aß peptide have been topical due to the critical role of this peptide in the pathogenesis of Alzheimer's disease. Many articles devoted to this process are available in the literature; however, none of them gives a detailed description of the mechanism of the process of generation of amyloids. Moreover, there are no reliable data on the influence of modified forms of Aß peptide on its amyloid formation. To appreciate the role of Aß aggregation in the pathogenesis of Alzheimer's disease and to develop a strategy for its treatment, it is necessary to have a well-defined description of the molecular mechanism underlying the formation of amyloids as well as the contribution of each intermediate to this process. We are convinced that a combined analysis of theoretical and experimental methods is a way for understanding molecular mechanisms of numerous diseases. Based on our experimental data and molecular modeling, we have constructed a general model of the process of amyloid formation by Aß peptide. Using the data described in our previous publications, we propose a model of amyloid formation by this peptide that differs from the generally accepted model. Our model can be applied to other proteins and peptides as well. According to this model, the main building unit for the formation of amyloid fibrils is a ring-like oligomer. Upon interaction with each other, ring-like oligomers form long fibrils of different morphology. This mechanism of generation of amyloid fibrils may be common for other proteins and peptides.

[Study of serum protein aggregation after treatment with urea]. / Issledovanie agregatsii belkov syvorotki krovi pod vliianiem mocheviny.

Gel chromatography and electrophoresis in polyacrylamide gel show that urea in vitro induces aggregation of blood proteins, with their content unchanged. The aggregation does not depend on the fibrinogen available. Comparison of the data on the effect of urea, DS-Na and thermal denaturation on the protein aggregation suggests that the aggregation is induced by local conformation transformations in the structure of certain protein molecules. At the same time, the data obtained do not permit neglecting the role of denaturation in the aggregation.