Abstract
Identifying nanomaterial-bio-interactions are imperative due to the broad introduction of nanoparticle (NP) applications and their distribution. Here, we demonstrate that silica NPs effect widespread protein aggregation in the soil nematode Caenorhabditis elegans ranging from induction of amyloid in nucleoli of intestinal cells to facilitation of protein aggregation in body wall muscles and axons of neural cells. Proteomic screening revealed that exposure of adult C. elegans with silica NPs promotes segregation of proteins belonging to the gene ontology (GO) group of "protein folding, proteolysis and stress response" to an SDS-resistant aggregome network. Candidate proteins in this group include chaperones, heat shock proteins and subunits of the 26S proteasome which are all decisively involved in protein homeostasis. The pathway of protein homeostasis was validated as a major target of silica NPs by behavioral phenotyping, as inhibitors of amyloid formation rescued NP-induced defects of locomotory patterns and egg laying. The analysis of a reporter worm for serotonergic neural cells revealed that silica NP-induced protein aggregation likewise occurs in axons of HSN neurons, where presynaptic accumulation of serotonin, e.g. disturbed axonal transport reduces the capacity for neurotransmission and egg laying. The results suggest that in C. elegans silica NPs promote a cascade of events including disturbance of protein homeostasis, widespread protein aggregation and inhibition of serotonergic neurotransmission which can be interrupted by compounds preventing amyloid fibrillation.
Recommended Citation
A. Scharf et al., "Anti-amyloid Compounds Protect From Silica Nanoparticle-induced Neurotoxicity In The Nematode C. Elegans," Nanotoxicology, vol. 10, no. 4, pp. 426 - 435, Taylor and Francis Group; Taylor and Francis, Apr 2016.
The definitive version is available at https://doi.org/10.3109/17435390.2015.1073399
Department(s)
Biological Sciences
Publication Status
Open Access
Keywords and Phrases
Aging; neurodegenerative disease; neurotoxicology; prevention; proteomics
International Standard Serial Number (ISSN)
1743-5404; 1743-5390
Document Type
Article - Journal
Document Version
Citation
File Type
text
Language(s)
English
Rights
© 2023 Taylor and Francis Group; Taylor and Francis, All rights reserved.
Publication Date
20 Apr 2016
PubMed ID
26444998
Comments
National Institutes of Health, Grant P40OD010440