Title
Reversing Aβ Fibrillation and Inhibiting Aβ Primary Neuronal Cell Toxicity Using Amphiphilic Polyphenylene Dendrons
Author
Siyuan Xiang, Jessica Wagner, Thorsten Luckerath, Klaus Mullen, David Y. W. Ng, Jana Hedrich, Tanja Weil
Year
2021
Journal
ADVANCED HEALTHCARE MATERIALS
Abstract
Uncontrolled amyloid-beta (Aβ) fibrillation leads to the deposition of neurotoxic amyloid plaques and is associated with Alzheimer's disease. Inhibiting Aβ monomer fibrillation and dissociation of the formed fibers is regarded as a promising therapeutic strategy. Here, amphiphilic polyphenylene dendrons (APDs) are demonstrated to interrupt Aβ assembly and reduce Aβ–cell interactions. Containing alternating negatively charged sulfonic acid and hydrophobic n-propyl peripheral groups, APDs bind to the secondary structure of the Aβ aggregates, inhibiting fibrillation and disassemble the already formed Aβ fibrils. APDs reveal vesicular cellular uptake in endosomes as well as cell compatibility for endothelial and neuronal cells, and significantly reduce Aβ-induced neuron cytotoxicity in vitro. Moreover, they are transported into the brain and successfully cross the blood–brain barrier after systemic application in mice, indicating their high potential to inhibit Aβ fibrillation in vivo, which can be beneficial for developing therapeutic strategy for Alzheimer's disease.
Instrument
J-1500
Keywords
amyloid-beta (Aβ), fibrillation, polyphenylene dendrons (APDs), therapeutic strategy, Alzheimer's disease