β-Hairpin Peptide Mimics Decrease Human Islet Amyloid Polypeptide (hIAPP) Aggregation.

Amyloid diseases are degenerative pathologies, highly prevalent today because they are closely related to aging, that have in common the erroneous folding of intrinsically disordered proteins (IDPs) which aggregate and lead to cell death. Type 2 Diabetes involves a peptide called human islet amyloid polypeptide (hIAPP), which undergoes a conformational change, triggering the aggregation process leading to amyloid aggregates and fibers rich in β-sheets mainly found in the pancreas of all diabetic patients. Inhibiting the aggregation of amyloid proteins has emerged as a relevant therapeutic approach and we have recently developed the design of acyclic flexible hairpins based on peptidic recognition sequences of the amyloid β peptide (Aβ) as a successful strategy to inhibit its aggregation involved in Alzheimer's disease.

Helical γ-Peptide Foldamers as Dual Inhibitors of Amyloid-β Peptide and Islet Amyloid Polypeptide Oligomerization and Fibrillization.

Type 2 diabetes (T2D) and Alzheimer's disease (AD) belong to the 10 deadliest diseases and are sorely lacking in effective treatments. Both pathologies are part of the degenerative disorders named amyloidoses, which involve the misfolding and the aggregation of amyloid peptides, hIAPP for T2D and Aβ for AD. While hIAPP and Aβ inhibitors have been essentially designed to target β-sheet-rich structures composing the toxic amyloid oligomers and fibrils of these peptides, the strategy aiming at trapping the non-toxic monomers in their helical native conformation has been rarely explored.

Evidence for different in vitro oligomerization behaviors of synthetic hIAPP obtained from different sources.

Type 2 diabetes is characterized by the aggregation of human islet amyloid polypeptide (hIAPP), from monomer to amyloid deposits that are made of insoluble fibrils. Discrepancies concerning the nature of formed species or oligomerization kinetics among reported in vitro studies on hIAPP aggregation process have been highlighted. In this work, we investigated if the sample itself could be at the origin of those observed differences.

A capillary zone electrophoresis method to investigate the oligomerization of the human Islet Amyloid Polypeptide involved in Type 2 Diabetes.

Type 2 diabetes is characterized by the aggregation of human Islet Amyloid Polypeptide (hIAPP) from monomer to large and insoluble fibrils. According to several recent studies, small soluble oligomers are now considered as potential toxic species. No monitoring tool has been to date reported to mimic in vitro the oligomerization process of hIAPP over time, although this would allow selecting candidate compounds that slow down or stop this pathological process.