Modulating human IAPP aggregation in type 2 diabetes: inhibitors, mechanisms, and translational challenges

Area of Science:

• Biochemistry
• Molecular Biology
• Endocrinology

Background:

• Islet amyloid polypeptide (IAPP) aggregation is a key pathological hallmark of type 2 diabetes (T2D).
• IAPP misfolding leads to toxic species, causing pancreatic β-cell dysfunction and loss.
• Understanding IAPP aggregation is crucial for developing T2D treatments.

Purpose of the Study:

• To review recent advancements in IAPP aggregation inhibitors.
• To explore various molecular strategies for modulating IAPP aggregation.
• To discuss the translational potential and future directions for IAPP inhibitors in T2D therapy.

Main Methods:

• Literature review of structural biology and chemical biology studies.
• Analysis of natural products, small synthetic molecules, peptide mimetics, antibody-based inhibitors, and supramolecular modulators.
• Examination of mechanistic insights and representative inhibitors.

Main Results:

• Significant progress has been made in understanding IAPP misfolding.
• Diverse classes of IAPP aggregation inhibitors have been developed.
• Mechanistic insights and translational potential of these inhibitors are increasingly understood.

Conclusions:

• IAPP aggregation inhibitors show promise as next-generation therapeutics for type 2 diabetes.
• Further research is needed to overcome challenges in clinical translation.
• Modulating IAPP aggregation offers a viable therapeutic strategy for T2D.