# Physiological Implications of Pancreatic Amyloid Polypeptide Aggregation and Its Inhibition by Melatonin

## TL;DR

Melatonin can prevent harmful protein clumps in diabetes and Alzheimer's by blocking toxic structures and aiding amyloid clearance.

## Contribution

Melatonin's multitarget therapeutic potential is revealed through its inhibition of hIAPP and Aβ aggregation and promotion of amyloid clearance.

## Key findings

- Melatonin disrupts hydrophobic interactions in hIAPP and Aβ, preventing toxic β-sheet formation.
- Melatonin promotes amyloid clearance via glymphatic and lymphatic systems and reduces Tau hyperphosphorylation.
- Melatonin protects neurons from oxidative damage and neuroinflammation caused by IAPP and Aβ.

## Abstract

Type 2 Diabetes (T2D) is characterized by the toxic aggregation of human islet amyloid polypeptide (hIAPP or amylin) within pancreatic β-cells. IAPP is also a neuropancreatic hormone that plays a significant role in Alzheimer’s disease (AD) by co-depositing with amyloid-beta (Aβ) and Tau, supporting the Type 3 Diabetes (T3D) hypothesis. Soluble IAPP accelerates Aβ aggregation through cross-seeding and causes neurotoxicity by impairing the blood–brain barrier and activating neuroinflammation. Melatonin inhibits these processes by disrupting hydrophobic interactions in both hIAPP and Aβ, preventing the formation of toxic β-sheet structures. Furthermore, melatonin promotes amyloid clearance via the glymphatic and lymphatic systems, protects neurons from oxidative damage, and reduces Tau hyperphosphorylation. This suggests that melatonin serves as a promising multitarget therapeutic agent for both metabolic and neurodegenerative disorders by modulating structural protein transformations.