Catalyst Awardee

Project Description

Cascade targeted multifunctional artificial molecular chaperone for synergistic treatment of Alzheimer's disease

Fan Huang, PhD |Institute of Radiation Medicine;  Jianfeng Liu, PhD; Jinjian Liu, PhD; Chunhua Ren, PhD; Yumin Zhang, PhD; Linzhu Su, PhD
Competition Sponsor: Chinese Academy of Medical Sciences
Awardee Year: 2022

Alzheimer’s disease (AD) is one of the most serious diseases that threaten human health in the 21st century. Because the pathogenesis of AD is extremely complex which was involved multiple factors including β-amyloid (Aβ) aggregation, imbalance of metal ion homeostasis and excessive oxidative brain injury, it is difficult for single-target drugs to meet the treatment needs of AD. Moreover, the current AD drugs still have shortcomings such as low blood-brain barrier penetration efficiency and poor targeting of AD lesions. Therefore, the project intends to develop a novel cascade targeted multifunctional artificial molecular chaperone through macromolecular self-assembly technology for the synergistic treatment of AD. This artificial molecular chaperone is composed of four parts, micelles with unique hydrophobic micro-domains on the surface which simulating natural molecular chaperones, bioactive small molecule drug in the core of micelles, blood brain barrier targeting peptide and AD lesion tissue targeting peptide modified on the outer layer of micelles. Through the mediation of dual-targeting peptides, this strategy can efficiently cross the blood-brain barrier and then selectively concentrate in the site of AD lesions, achieving the effect of “cascade targeting”. At the same time, by simulating the hydrophobic domain of natural molecular chaperones, the surface hydrophobic micro-domains of micelles can effectively inhibit the aggregation of Aβ, and the combined small-molecule drugs can regulate metal ion homeostasis and reduce oxidative damage, thereby achieving the purpose of “multi-target therapy”. This project will open up new avenues for targeted and synergistic treatment of AD.


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