Insights from Caenorhabditis elegans on the role of metals in neurodegenerative diseases

Martinez-Finley, Ebany J.; Ávila, Daiana Silva; Chakraborty, Sudipta; Aschner, Michael

doi:10.1039/c0mt00064g

Cited by 36 publications

(26 citation statements)

References 103 publications

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“…Uric acid can scavenge free radicals, nitrogen-oxygen-based radicals, such as peroxynitrite and its derivatives, and chelate iron [48]. In vitro and vivo studies, it is suggested that uric acid is a powerful radical scavenger of neurons [46][47][48].…”

Section: Discussionmentioning

confidence: 98%

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Inverse Association Between Serum Uric Acid Levels and Alzheimer’s Disease Risk

Hou

et al. 2015

Mol Neurobiol

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The association between Alzheimer's disease and uric acid levels had gained great interest in recent years, but there was still lack of definite evidence. A systematic review and meta-analysis of relevant studies was performed to comprehensively estimate the association. Relevant studies published before October 26, 2014, were searched in PubMed, Embase, and China Biology Medicine (CBM) databases. Study-specific data were combined using random-effects or fixed-effects models of meta-analysis according to between-study heterogeneity. Twenty-four studies (21 case-control and 3 cohort studies) were finally included into the meta-analysis. Those 21 case-control studies included a total of 1128 cases of Alzheimer's disease and 2498 controls without Alzheimer's disease. Those 3 cohort studies included a total of 7327 participants. Meta-analysis showed that patients with Alzheimer's disease had lower levels of uric acid than healthy controls (weighted mean difference (WMD) = -0.77 mg/dl, 95% CI -2.28 to -0.36, P = 0.0002). High serum uric acid levels were significantly associated with decreased risk of Alzheimer's disease (risk ratio (RR) = 0.66, 95% CI 0.52-0.85, P = 0.001). There was low risk of publication bias in the meta-analysis. There is an inverse association between serum uric acid levels and Alzheimer's disease. High serum uric acid level is a protective factor of Alzheimer's disease.

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Section: Discussionmentioning

confidence: 98%

“…Cerebral tissue is susceptible to oxidative damage because of its high oxygen requirement for metabolism, the high level of polyunsaturated fatty acid, and the low concentration of antioxidant resources [46,47]. The effect of serum uric acid upon the Alzheimer's disease has been widely studied.…”

Section: Discussionmentioning

confidence: 99%

Inverse Association Between Serum Uric Acid Levels and Alzheimer’s Disease Risk

Hou

et al. 2015

Mol Neurobiol

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“…Exposure of laboratory-adapted C . elegans to toxic levels of copper sulfate was observed to reduce brood size and life span while slowing development [18–20]. …”

Section: Introductionmentioning

confidence: 99%

Copper Oxide Nanoparticles Impact Several Toxicological Endpoints and Cause Neurodegeneration in Caenorhabditis elegans

et al. 2016

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Engineered nanoparticles are becoming increasingly incorporated into technology and consumer products. In 2014, over 300 tons of copper oxide nanoparticles were manufactured in the United States. The increased production of nanoparticles raises concerns regarding the potential introduction into the environment or human exposure. Copper oxide nanoparticles commonly release copper ions into solutions, which contribute to their toxicity. We quantified the inhibitory effects of both copper oxide nanoparticles and copper sulfate on C. elegans toxicological endpoints to elucidate their biological effects. Several toxicological endpoints were analyzed in C. elegans, including nematode reproduction, feeding behavior, and average body length. We examined three wild C. elegans isolates together with the Bristol N2 laboratory strain to explore the influence of different genotypic backgrounds on the physiological response to copper challenge. All strains exhibited greater sensitivity to copper oxide nanoparticles compared to copper sulfate, as indicated by reduction of average body length and feeding behavior. Reproduction was significantly reduced only at the highest copper dose, though still more pronounced with copper oxide nanoparticles compared to copper sulfate treatment. Furthermore, we investigated the effects of copper oxide nanoparticles and copper sulfate on neurons, cells with known vulnerability to heavy metal toxicity. Degeneration of dopaminergic neurons was observed in up to 10% of the population after copper oxide nanoparticle exposure. Additionally, mutants in the divalent-metal transporters, smf-1 or smf-2, showed increased tolerance to copper exposure, implicating both transporters in copper-induced neurodegeneration. These results highlight the complex nature of CuO nanoparticle toxicity, in which a nanoparticle-specific effect was observed in some traits (average body length, feeding behavior) and a copper ion specific effect was observed for other traits (neurodegeneration, response to stress).

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“…elegans studies have also confirmed that manganese exposure may have an additive effect on DAergic neurodegeneration in neurons containing α-synuclein protein aggregates. Various labs have concluded that the C. elegans SMF-1 transporter, an analogue of the divalent metal transporter (DMT-1) found in humans, is important in the degeneration of these neurons [146,147,149,150]. Results in C. elegans indicate that this transporter plays a significant role in neurotoxicity by transporting manganese into the cell where it can induce numerous intracellular changes.…”

Section: Manganese-containing Dithiocarbamate Fungicidesmentioning

confidence: 99%