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

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 Aβ 42 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.

Nanosilver Mitigates Biofilm Formation via FapC Amyloidosis Inhibition

“…This suggests that the AgNPs inhibited FapC fibrillization by sequestering monomeric FapC (Figure 2C). The secondary structure contents of the AgNCs + FapC complexes appeared to be between that for FapC monomers and fibrils, indicating limited formation of cross‐β amyloid fibrils (Figure 2B,C). Similarly, the zeta potential of AgNCs + FapC complexes was −25 mV, compared to a zeta potential of −36 mV for FapC amyloid fibrils and +30 mV for AgNCs, indicating the presence of fibrils in the AgNCs + FapC complexes (Figure 2D).…”

“…Images were processed via ENVI 4.8 software. AgNPs alone were used as a control and a spectral library generated from AgNPs was averaged to single mean spectra and scanned against AgNP‐treated bacterial samples . No scattering spectra were observed from untreated bacterial control.…”

“…Atomistic DMD simulations were applied to simulate FapC aggregation. DMD is a rapid and predictive molecular dynamics algorithm which has been used to study protein aggregation and nano–bio interface, and detailed description of the DMD algorithm can be found elsewhere . Based on the previous study, an AgNC comprising 38 silver atoms was reconstructed with a diameter of ≈1 nm.…”

“…Within the context of amyloid inhibition, the catalytic or inhibitory effects of metal nanoparticles depend upon the surface functionalization, metal core, and size of the particles . For example, gold nanoparticles (AuNPs) capped with citrate or polyethylene glycol (PEG) accelerated amyloidosis, while AuNPs coated with milk proteins inhibited the fibrillization of amyloid proteins . Larger metal nanoparticles elicited a stronger inhibitory effect on amyloidosis than smaller nanoparticles of similar surface functionalization .…”

Naphthalene monoimide derivative ameliorates amyloid burden and cognitive decline in a transgenic mouse model of Alzheimer’s disease

“…The sequential proteolytic cleavages of APP by β and γ-secretases produce Aβ peptides of variable lengths (36-43 amino acids)(2,40). Among these Aβ peptides, Aβ42 is highly aggregation-prone and undergoes misfolding and ordered the assembly to form neurotoxic amyloid plaques which contribute to multifaceted toxicity including plasma membrane disruption, synaptic dysfunction, memory impairment, cognitive decline and neuronal loss in the AD brain(41)(42)(43)(44)(45)(46)(47). The modulation of severe amyloid burden and associated neurotoxicity to improve cognitive functions is a gigantic challenge to research and clinical community.…”