Unknown

Dataset Information

0

The Role of Glycation on the Aggregation Properties of IAPP.


ABSTRACT: Epidemiological evidence shows an increased risk for developing Alzheimer's disease in people affected by diabetes, a pathology associated with increased hyperglycemia. A potential factor that could explain this link could be the role that sugars may play in both diseases under the form of glycation. Contrary to glycosylation, glycation is an enzyme-free reaction that leads to formation of toxic advanced glycation end-products (AGEs). In diabetes, the islet amyloid polypeptide (IAPP or amylin) is found to be heavily glycated and to form toxic amyloid-like aggregates, similar to those observed for the A? peptides, often also heavily glycated, observed in Alzheimer patients. Here, we studied the effects of glycation on the structure and aggregation properties of IAPP with several biophysical techniques ranging from fluorescence to circular dichroism, mass spectrometry and atomic force microscopy. We demonstrate that glycation occurs exclusively on the N-terminal lysine leaving the only arginine (Arg11) unmodified. At variance with recent studies, we show that the dynamical interplay between glycation and aggregation affects the structure of the peptide, slows down the aggregation process and influences the aggregate morphology.

SUBMITTER: Milordini G 

PROVIDER: S-EPMC7284065 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

altmetric image

Publications

The Role of Glycation on the Aggregation Properties of IAPP.

Milordini Giulia G   Zacco Elsa E   Percival Matthew M   Puglisi Rita R   Dal Piaz Fabrizio F   Temussi Pierandrea P   Pastore Annalisa A  

Frontiers in molecular biosciences 20200603


Epidemiological evidence shows an increased risk for developing Alzheimer's disease in people affected by diabetes, a pathology associated with increased hyperglycemia. A potential factor that could explain this link could be the role that sugars may play in both diseases under the form of glycation. Contrary to glycosylation, glycation is an enzyme-free reaction that leads to formation of toxic advanced glycation end-products (AGEs). In diabetes, the islet amyloid polypeptide (IAPP or amylin) i  ...[more]

Similar Datasets

| S-EPMC7022431 | biostudies-literature
| S-EPMC4725907 | biostudies-literature
| S-EPMC6212334 | biostudies-literature
| S-EPMC5446405 | biostudies-literature
| S-EPMC6162064 | biostudies-literature
| S-EPMC7895988 | biostudies-literature
| S-EPMC8341728 | biostudies-literature
| S-EPMC7275713 | biostudies-literature
| S-EPMC4944530 | biostudies-literature
| S-EPMC4075326 | biostudies-literature