Study of Biomolecular Interactions of Mitochondrial Proteins Related to Alzheimer's Disease: Toward Multi-Interaction Biomolecular Processes.

Progressive mitochondrial dysfunction due to the accumulation of amyloid beta (A beta) peptide within the mitochondrial matrix represents one of the key characteristics of Alzheimer's disease (AD) and appears already in its early stages. Inside the mitochondria, A beta interacts with a number of biomolecules, including cyclophilin D (cypD) and 17 beta-hydroxysteroid dehydrogenase type 10 (17 beta-HSD10), and affects their physiological functions. However, despite intensive ongoing research, the exact mechanisms through which A beta impairs mitochondrial functions remain to be explained. In this work, we studied the interactions of A beta with cypD and 17 beta-HSD10 in vitro using the surface plasmon resonance (SPR) method and determined the kinetic parameters (association and dissociation rates) of these interactions. This is the first work which determines all these parameters under the same conditions, thus, enabling direct comparison of relative affinities of A beta to its mitochondrial binding partners. Moreover, we used the determined characteristics of the individual interactions to simulate the concurrent interactions of A beta with cypD and 17 beta-HSD10 in different model situations associated with the progression of AD. This study not only advances the understanding of A beta-induced processes in mitochondria during AD, but it also provides a new perspective on research into complex multi-interaction biomolecular processes in general.