Inhibition of amyloid beta toxicity in zebrafish with a chaperone-gold nanoparticle dual strategy

Ibrahim Javed, Guotao Peng, Yanting Xing, Tianyu Yu, Mei Zhao, Aleksandr Kakinen, Ava Faridi, Clare L. Parish, Feng Ding (), Thomas P. Davis (), Pu Chun Ke () and Sijie Lin ()
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Ibrahim Javed: Monash University
Guotao Peng: Tongji University
Yanting Xing: Clemson University
Tianyu Yu: Tongji University
Mei Zhao: Tongji University
Aleksandr Kakinen: Monash University
Ava Faridi: Monash University
Clare L. Parish: The University of Melbourne
Feng Ding: Clemson University
Thomas P. Davis: Monash University
Pu Chun Ke: Monash University
Sijie Lin: Tongji University

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: Abstract Alzheimer’s disease (AD) is the most prevalent form of neurodegenerative disorders, yet no major breakthroughs have been made in AD human trials and the disease remains a paramount challenge and a stigma in medicine. Here we eliminate the toxicity of amyloid beta (Aβ) in a facile, high-throughput zebrafish (Danio rerio) model using casein coated-gold nanoparticles (βCas AuNPs). βCas AuNPs in systemic circulation translocate across the blood brain barrier of zebrafish larvae and sequester intracerebral Aβ42 and its elicited toxicity in a nonspecific, chaperone-like manner. This is evidenced by behavioral pathology, reactive oxygen species and neuronal dysfunction biomarkers assays, complemented by brain histology and inductively coupled plasma-mass spectroscopy. We further demonstrate the capacity of βCas AuNPs in recovering the mobility and cognitive function of adult zebrafish exposed to Aβ. This potent, safe-to-use, and easy-to-apply nanomedicine may find broad use for eradicating toxic amyloid proteins implicated in a range of human diseases.

Date: 2019
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DOI: 10.1038/s41467-019-11762-0

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