title: Amyloid formation in heterogeneous environments: islet amyloid polypeptide glycosaminoglycan interactions.
abstract: Amyloid formation plays an important role in a broad range of diseases, and the search for amyloid inhibitors is an active area of research. Amyloid formation takes places in a heterogeneous environment in vivo with the potential for interactions with membranes and with components of the extracellular matrix. Naturally occurring amyloid deposits are associated with sulfated proteoglycans and other factors. However, the vast majority of in vitro assays of amyloid formation and amyloid inhibition are conducted in homogeneous solution where the potential for interactions with membranes or sulfated proteoglycans is lacking and it is possible that different results may be obtained in heterogeneous environments. We show that variants of islet amyloid polypeptide (IAPP), which are non-amyloidogenic in homogeneous solution, can be readily induced to form amyloid in the presence of glycosaminoglycans (GAGs). GAGs are found to be more effective than anionic lipid vesicles at inducing amyloid formation on a per-charge basis. Several known inhibitors of IAPP amyloid formation are shown to be less effective in the presence of GAGs.
authors.affiliation: Department of Chemistry, State University of New York at Stony Brook, Stony Brook, NY 11794-3400, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Ping
authors.initials: P
authors.lastname: Cao
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Raleigh
mesh_terms: D000595:Amino Acid Sequence; D006025:Glycosaminoglycans / Q000378:metabolism*; D058228:Islet Amyloid Polypeptide / Q000378:metabolism*; D007700:Kinetics; D008969:Molecular Sequence Data; D011485:Protein Binding; D055503:Protein Multimerization
chemical_list: D006025:Glycosaminoglycans; D058228:Islet Amyloid Polypeptide