title: Mechanistic Contributions of Biological Cofactors in Islet Amyloid Polypeptide Amyloidogenesis.
abstract: Type II diabetes mellitus is associated with the deposition of fibrillar aggregates in pancreatic islets. The major protein component of islet amyloids is the glucomodulatory hormone islet amyloid polypeptide (IAPP). Islet amyloid fibrils are virtually always associated with several biomolecules, including apolipoprotein E, metals, glycosaminoglycans, and various lipids. IAPP amyloidogenesis has been originally perceived as a self-assembly homogeneous process in which the inherent aggregation propensity of the peptide and its local concentration constitute the major driving forces to fibrillization. However, over the last two decades, numerous studies have shown a prominent role of amyloid cofactors in IAPP fibrillogenesis associated with the etiology of type II diabetes. It is increasingly evident that the biochemical microenvironment in which IAPP amyloid formation occurs and the interactions of the polypeptide with various biomolecules not only modulate the rate and extent of aggregation, but could also remodel the amyloidogenesis process as well as the structure, toxicity, and stability of the resulting fibrils.
authors.affiliation: Department of Chemistry, Pharmaqam, University of Quebec in Montreal, Montreal, QC, Canada H3C 3P8 ; Quebec Network for Research on Protein Function, Structure, and Engineering (PROTEO), Canada.
authors.forename: Phuong Trang
authors.initials: PT
authors.lastname: Nguyen
authors.affiliation: Department of Chemistry, Pharmaqam, University of Quebec in Montreal, Montreal, QC, Canada H3C 3P8 ; Quebec Network for Research on Protein Function, Structure, and Engineering (PROTEO), Canada ; Biophysics Unit (CSIC, UPV/EHU) and Department of Biochemistry and Molecular Biology, Faculty of Science and Technology, University of the Basque Country, 48080 Bilbao, Spain.
authors.forename: Nagore
authors.initials: N
authors.lastname: Andraka
authors.affiliation: Department of Chemistry, Pharmaqam, University of Quebec in Montreal, Montreal, QC, Canada H3C 3P8 ; Quebec Network for Research on Protein Function, Structure, and Engineering (PROTEO), Canada.
authors.forename: Carole Anne
authors.initials: CA
authors.lastname: De Carufel
authors.affiliation: Department of Chemistry, Pharmaqam, University of Quebec in Montreal, Montreal, QC, Canada H3C 3P8 ; Quebec Network for Research on Protein Function, Structure, and Engineering (PROTEO), Canada.
authors.forename: Steve
authors.initials: S
authors.lastname: Bourgault
mesh_terms: D000682:Amyloid / Q000378:metabolism*; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D006801:Humans; D058228:Islet Amyloid Polypeptide / Q000096:biosynthesis*; D007515:Islets of Langerhans / Q000378:metabolism*
chemical_list: D000682:Amyloid; D058228:Islet Amyloid Polypeptide