Amyloid Targeting Red Emitting AIE Dots for Diagnostic and Therapeutic Application against Alzheimer's Disease.

Abstract

The emergence of neurodegenerative diseases is connected to several pathogenic factors, including metal ions, amyloidogenic proteins, and reactive oxygen species. Recent studies suggest that cytotoxicity is caused by the small, dynamic, and metastable nature of early stage oligomeric species. This work introduces a small molecule-based red-emitting probe with smart features such as increased reactivities against multiple targets, metal-free amyloid-β (Aβ), and metal-bound amyloid-β (Aβ), and most importantly, early stage oligomeric species which are associated with the most common and widespread type of dementia, Alzheimer's disease (AD). Theoretical analyses like molecular dynamics simulation and molecular docking were performed to confirm the reactivity of the molecule toward Aβ and found some excellent interactions between the molecule and the peptide. The in vitro and cellular studies demonstrated that this highly biocompatible molecule effectively reduces the structural damage to mitochondria while shielding cells from apoptosis, scavenges ROS (reactive oxygen species), and attenuates multifaceted amyloid toxicity.