Studies of the Process of Amyloid Formation by Aβ Peptide.

Abstract

Studies of the process of amyloid formation by Aβ 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 Aβ peptide on its amyloid formation. To appreciate the role of Aβ 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 Aβ 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.