Cobalt nanoparticles induce mitochondrial damage and ?-amyloid toxicity via the generation of reactive oxygen species

Exposure to cobalt nanoparticles (CoNPs) has been associated with neurodegenerative disorders, while the mitochondrial-associated mechanisms that mediate their neurotoxicity have yet to be fully characterized. In this study, we reported that CoNPs exposure reduced the survival and lifespan in the nematodes, Caenorhabditis elegans (C. elegans). Moreover, exposure to CoNPs aggravated the induction of paralysis and the aggregation of beta-amyloid (A beta). These effects were accompanied by reactive oxygen species (ROS) overproduction, ATP reduc-tion as well as mitochondrial fragmentation. Dynamin-related protein 1 (drp-1) activation and ensuing mito-chondrial fragmentation have been shown to be associated with CoNPs-reduced survival. In order to address the role of mitochondrial damage and ROS production in CoNPs-induced A beta toxicity, the mitochondrial reactive oxygen species scavenger mitoquinone (Mito Q) was used. Our results showed that Mito Q pretreatment alle-viated CoNPs-induced ROS generation, rescuing mitochondrial dysfunction, thereby lessening the CoNPs-induced A beta toxicity. Taken together, we show for the first time, that increasing of ROS and the upregulation of drp-1 lead to CoNPs-induced A beta toxicity. Our novel findings provide in vivo evidence for the mechanisms of environmental toxicant-induced A beta toxicity, and can afford new modalities for the prevention and treatment of CoNPs-induced neurodegeneration.

Automated summary

Exposure to cobalt nanoparticles (CoNPs) is associated with neurodegenerative disorders, and the mitochondrial mechanisms underlying their neurotoxicity have not been fully characterized. This study found that CoNPs exposure reduced survival and lifespan in nematodes. Additionally, CoNPs exposure aggravated paralysis and beta-amyloid aggregation, accompanied by reactive oxygen species overproduction, ATP reduction, and mitochondrial fragmentation.