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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Alzheimer Disease / drug therapy*
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Alzheimer Disease / pathology
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Amyloid beta-Peptides / antagonists & inhibitors*
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Amyloid beta-Peptides / metabolism
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Amyloid beta-Peptides / toxicity
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Animals
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Behavior, Animal / drug effects
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Blood-Brain Barrier / metabolism
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Blood-Brain Barrier / pathology
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Caseins / administration & dosage
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Caseins / pharmacokinetics
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Chelating Agents / administration & dosage*
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Chelating Agents / pharmacokinetics
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Cognition / drug effects
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Disease Models, Animal
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Drug Carriers / chemistry*
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Drug Carriers / pharmacokinetics
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Embryo, Nonmammalian
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Female
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Gold / chemistry
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High-Throughput Screening Assays
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Humans
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Male
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Metal Nanoparticles / chemistry*
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Peptide Fragments / antagonists & inhibitors*
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Peptide Fragments / metabolism
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Peptide Fragments / toxicity
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Permeability
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Treatment Outcome
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Zebrafish
Substances
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Amyloid beta-Peptides
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Caseins
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Chelating Agents
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Drug Carriers
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Peptide Fragments
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amyloid beta-protein (1-42)
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Gold