title: A mechanistic approach for islet amyloid polypeptide aggregation to develop anti-amyloidogenic agents for type-2 diabetes.
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.
authors.affiliation: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh 202002, India.
authors.forename: Ejaz
authors.initials: E
authors.lastname: Ahmad
authors.forename: Aqeel
authors.initials: A
authors.lastname: Ahmad
authors.forename: Saurabh
authors.initials: S
authors.lastname: Singh
authors.forename: Md
authors.initials: M
authors.lastname: Arshad
authors.forename: Abdul Hameed
authors.initials: AH
authors.lastname: Khan
authors.forename: Rizwan Hasan
authors.initials: RH
authors.lastname: Khan
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology / Q000517:prevention & control*; D019143:Evolution, Molecular; D006801:Humans; D058228:Islet Amyloid Polypeptide / Q000378:metabolism*; D007515:Islets of Langerhans / Q000378:metabolism / Q000473:pathology*; D008969:Molecular Sequence Data; D017510:Protein Folding; D055503:Protein Multimerization; D011498:Protein Precursors / Q000378:metabolism*; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary
chemical_list: D058228:Islet Amyloid Polypeptide; D011498:Protein Precursors