Title : Unraveling the Molecular Mechanism of the Peptide Aggregation by Characterizing the Invisible Intermediates Responsible for Alzheimer and Diabetics Diseases Using NMR Spectroscopy
The mis-folding and the subsequent aggregation of the peptide such as Abeta40 (40 amino acids) and hIAPP (37 amino acids) have been implicated in the pathogenesis of the diseases such as Alzheimer and Diabetics, respectively. Despite, the differences in the manifestation of the diseases, the underlying molecular mechanism of these disease follows a defined pattern. At the outset, the free peptide remains unstructured, but in the due course of time, the peptide oligomerizes into micellar structures, which elongates into long fibrillar structures. The long held belief that the fibrils are solely responsible for the lysis of the bio-membrane and the subsequent cell death, has been thwarted by the recent studies, which suggest that, it is the invisible, lowly populated, intermediate states of the peptides or oligomers, are responsible for the cell death. We used a series of NMR experiments such as CPMG (Carr Purcell Meiboom Gill spin echo)-relaxation dispersion experiment, DEST (Dark/invisible state exchange saturation transfer experiment) and Off-resonance NMR to understand the molecular mechanism of the initial stages of the aggregation of Abeta40 and hIAPP.