PUBLICATION
Inhibition of amyloid beta toxicity in zebrafish with a chaperone-gold nanoparticle dual strategy
- Authors
- Javed, I., Peng, G., Xing, Y., Yu, T., Zhao, M., Kakinen, A., Faridi, A., Parish, C.L., Ding, F., Davis, T.P., Ke, P.C., Lin, S.
- ID
- ZDB-PUB-190826-4
- Date
- 2019
- Source
- Nature communications 10: 3780 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Alzheimer Disease/drug therapy*
- Alzheimer Disease/pathology
- Amyloid beta-Peptides/antagonists & inhibitors*
- Amyloid beta-Peptides/metabolism
- Amyloid beta-Peptides/toxicity
- Animals
- Behavior, Animal/drug effects
- Blood-Brain Barrier/metabolism
- Blood-Brain Barrier/pathology
- Caseins/administration & dosage
- Caseins/pharmacokinetics
- Chelating Agents/administration & dosage*
- Chelating Agents/pharmacokinetics
- Cognition/drug effects
- Disease Models, Animal
- Drug Carriers/chemistry*
- Drug Carriers/pharmacokinetics
- Embryo, Nonmammalian
- Female
- Gold/chemistry
- High-Throughput Screening Assays
- Humans
- Male
- Metal Nanoparticles/chemistry*
- Peptide Fragments/antagonists & inhibitors*
- Peptide Fragments/metabolism
- Peptide Fragments/toxicity
- Permeability
- Treatment Outcome
- Zebrafish
- PubMed
- 31439844 Full text @ Nat. Commun.
Citation
Javed, I., Peng, G., Xing, Y., Yu, T., Zhao, M., Kakinen, A., Faridi, A., Parish, C.L., Ding, F., Davis, T.P., Ke, P.C., Lin, S. (2019) Inhibition of amyloid beta toxicity in zebrafish with a chaperone-gold nanoparticle dual strategy. Nature communications. 10:3780.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping