Abstract
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 Aβ in order to reproduce its pathologic effects. Several studies reveal that among Aβ fragments, Aβ(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 Aβ(25-35) in SDS combining CD and NMR spectroscopies at different times. From the solved structures, it emerges that Aβ(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 Aβ(25-35) in a micellar system, favoring the stabilization and the formation of a soluble helix conformation.