A self-destructive nanosweeper that captures and clears amyloid β-peptides

• Published in: Nature communications Vol. 9; no. 1; pp. 1802 - 12
• Main Authors: Luo, Qiang, Lin, Yao-Xin, Yang, Pei-Pei, Wang, Yi, Qi, Guo-Bin, Qiao, Zeng-Ying, Li, Bing-Nan, Zhang, Kuo, Zhang, Jing-Ping, Wang, Lei, Wang, Hao
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 04-05-2018; Nature Publishing Group; Nature Portfolio
• Subjects: 14; 14/19; 14/34; 140/131; 140/58; 147/143; 639/301/54/152; 639/638/298/54; 639/925/352/152; Alzheimer Disease - genetics; Alzheimer Disease - metabolism; Alzheimer Disease - physiopathology; Alzheimer's disease; Amino Acid Sequence; Amyloid beta-Peptides - chemistry; Amyloid beta-Peptides - metabolism; Animals; Autophagy; Autophagy - drug effects; Beclin-1 - chemistry; Brain - drug effects; Brain - metabolism; Brain - ultrastructure; Cell Line, Tumor; Chitosan - chemistry; Cytotoxicity; Disease Models, Animal; Homeostasis; Humanities and Social Sciences; Humans; Hydrogen bonding; Maze Learning - drug effects; Mice, Inbred C57BL; Mice, Transgenic; multidisciplinary; Nanoparticles - administration & dosage; Nanoparticles - chemistry; Nanoparticles - ultrastructure; Peptides; Peptides - administration & dosage; Peptides - chemistry; Peptides - metabolism; Phagocytosis; Plaque, Amyloid - chemistry; Plaque, Amyloid - metabolism; Polyethylene Glycols - chemistry; Polymers; Rodents; Science; Science (multidisciplinary); Senile plaques; Toxicity; Transgenic mice; β-Amyloid
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-018-04255-z

Cerebral amyloid β-peptide (Aβ) accumulation resulting from an imbalance between Aβ production and clearance is one of the most important causes in the formation of Alzheimer’s disease (AD). In order to preserve the maintenance of Aβ homeostasis and have a notable AD therapy, achieving a method to clear up Aβ plaques becomes an emerging task. Herein, we describe a self-destructive nanosweeper based on multifunctional peptide-polymers that is capable of capturing and clearing Aβ for the effective treatment of AD. The nanosweeper recognize and bind Aβ via co-assembly through hydrogen bonding interactions. The Aβ-loaded nanosweeper enters cells and upregulates autophagy thus promoting the degradation of Aβ. As a result, the nanosweeper decreases the cytotoxicity of Aβ and rescues memory deficits of AD transgenic mice. We believe that this resourceful and synergistic approach has valuable potential as an AD treatment strategy.
Cerebral amyloid β-peptide accumulation is a causative factor in Alzheimer’s Disease. Here the authors design a 'nanosweeper' that binds amyloid β-peptide and induces autophagy to clear the accumulated plagues.