Abstract
Type-2 diabetes mellitus (DM-2) is a conformational disease involving intrinsically disordered islet amyloid polypeptide (IAPP), in which a structural transition from physiological polypeptide to pathological deposits takes place. Different factors acquired or inherited, contribute to endoplasmic reticulum stress and/or impair mitochondrial function which leads to conformational changes in IAPP intermediates and ultimately produces oligomers of an anti-parallel crossed β-pleated sheets that eventually accumulate as space-occupying lesions within the islets. Clusters of IAPP monomers form a pore which is linked to channel-like behavior in planar bilayers, indicating that these oligomeric IAPP pores could become incorporated into membranes and alter its barrier properties. Identification of nucleating residues and the residues responsible for this oligomeric tendency could improve understanding of structure–function relationships as well as the molecular mechanism of folding and aggregation of IAPP contributing to the onset of DM-2. A combination of biological, chemical or physical approaches is required to be extensively pursued for the development of a successful anti-amyloidogenic agent to prevent this malady. Exploring the hypothesis of π-stacking may be a better option to control IAPP aggregation if researchers go through the mechanism of π–π interaction, which provides entropy driven energy and direction for self-assembly to control amyloidogenic aggregation.
► Aggregation is the most riveting topic as most of the diseases are concerned with this phenomenon. ► In DM-2 a structural transition from physiological IAPP to pathological deposits takes place. ► IAPP aggregation (amyloidosis) takes place due to different acquired or inherited factors. ► This is compilation of multidisciplinary approaches to translate into new research opportunities. ► It will abet the communication between biologists and chemists to develop agents against amyloids.