Monitoring the Conformational Changes of the A beta(25-35) Peptide in SDS Micelles: A Matter of Time

Alzheimer's disease is a neurodegenerative disease characterized by the formation of amyloid plaques constituted prevalently by amyloid peptides. Due to the well-known challenges related to the study in solution of these peptides, several membrane-mimicking systems such as micelle constituted by detergent-i.e., DPC and SDS-have been deeply investigated. Additionally, the strategy of studying short fragments instead of the full-length peptide turned out to be advantageous in exploring the structural properties of the different moieties in A beta in order to reproduce its pathologic effects. Several studies reveal that among A beta fragments, A beta(25-35) is the shortest fragment able to reproduce the aggregation process. To enrich the structural data currently available, in the present work we decided to evaluate the conformational changes adopted by A beta(25-35) in SDS combining CD and NMR spectroscopies at different times. From the solved structures, it emerges that A beta(25-35) passes from an unordered conformation at the time of the constitution of the system to a more ordered and energetically favorable secondary structure at day 7, which is kept for 2 weeks. These preliminary data suggest that a relatively long time affects the kinetic in the aggregation process of A beta(25-35) in a micellar system, favoring the stabilization and the formation of a soluble helix conformation.