The conversion of a protein from its native conformation to the pathogenic form is a critical event in the pathogenesis of several neurodegenerative disorders such as Alzheimer’s (AD), Parkinson’s, and Huntington’s diseases, along with type II diabetic mellitus. Although there are several reports on the mechanism of protein aggregation, the actual conformation playing a part in the pathogenicity is yet unclear. Accordingly, the present study summarizes the early pathogenic conformation resulting in several protein aggregations. It is well-documented that a pre-molten globule (MG) structure appears at the early stages of some proteins. Pre-MG is one of the intermediate structures, which is formed during some protein unfolding processes. In addition, it is shown that the pre-molten structure is more flexible than the mature MG one and thus, protein easily rearranges to form amyloid fibrils in this conformation. Therefore, protein aggregation is halted by preventing the pre-MG structure. The strategy of protein aggregation prevention has profound implications in fighting the devastating disorder.
The generic unfolding of a biomimetic polymer during force spectroscopy
