Copper Status in Alzheimer’s Disease and Other Neurodegenerative Disorders 2013

Squitti, Rosanna; Hoogenraad, T. U.; Brewer, George J.; Bush, Ashley I.; Polimanti, Renato

doi:10.1155/2013/838274

Cited by 3 publications

(2 citation statements)

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“…S-nitrosylation of protein targets has been associated with neurodegenerative disorders including Alzheimer's and Parkinson's (Brown, 2010). Cu(I) dysfunction has also been observed in neurodegeneration (Squitti et al, 2013). The ‘metal-based neurodegeneration hypothesis’ is based on the observation that the generation of oxidative stress results from the production of reactive oxygen (ROS) and nitrogen species (RNS) by redox-active metal ions including Cu(I).…”

Section: Discussionmentioning

confidence: 99%

Copper disrupts S-nitrosothiol signaling in activated BV2 microglia

Rossi-George¹,

Guo

2016

Neurochemistry International

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Microglia, the primary resident immune cells of the central nervous system (CNS), respond rapidly to pathogens and injury by secreting immune mediators including nitric oxide (NO). The reaction of NO with the anti-oxidant glutathione forms S-nitrosoglutathione (GSNO), the major pool of biologic NO in the body. GSNO is degraded by GSNO reductase (GSNOR). Recently, we have shown that copper (Cu(I)) inhibits the release of NO in lipopolysaccharide (LPS)-stimulated BV2 microglia and induces BV2 microglia to acquire a mixed a profile with both pro- and anti-inflammatory characteristics. Since GSNOR is the critical enzyme in GSNO metabolism, we sought to determine whether Cu(I) affects GSNOR activity and S-nitrosothiol (SNO) accumulation in activated BV2 microglia. Our results show that GSNOR protein expression is reduced by Cu(I) treatment in LPS-stimulated BV2 microglia. Our results also show a decrease in S-nitrosothiol content despite a reduced GSNOR expression. This effect is most likely due to Cu(I) reacting with the central thiol of the S-NO bond resulting in the degradation of SNO. A dose of 1 μM Cu(I) did not affect SNO protein accumulation in LPS-stimulated BV2 microglia, however, a dose of 100 μM Cu(I) inhibited SNO protein in accordance with inhibition of S-nitrosothiols. These data provide direct evidence that Cu(I) disrupts S-nitrosothiol homeostasis and NO metabolism, and, thus, provide new insights into the mechanisms involved in microglia-mediated-CNS disorders.

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Section: Discussionmentioning

confidence: 99%

Copper disrupts S-nitrosothiol signaling in activated BV2 microglia

Rossi-George¹,

Guo

2016

Neurochemistry International

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“…Importantly, CTR1 has been found to be over-expressed in Alzheimer′s disease and a variety of cancers. It then has been explored as a novel target for tumor imaging and therapy in recent years [ 8 , 9 , 10 , 11 , 12 , 13 , 14 ]. For example, 64 CuCl 2 , as the substrate of CTR1, has been demonstrated as a potential positron emission tomography (PET) tracer for imaging animal models with melanoma, liver cancer, and prostate cancer [ 10 , 12 , 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Pilot Study of 64CuCl2 for PET Imaging of Inflammation

et al. 2018

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Copper(II) ion (Cu2+) is the essential element for numerous pathophysiological processes in vivo. Copper transporter 1 (CTR1) is mainly responsible for maintaining Cu2+ accumulation in cells, which has been found to be over-expressed in inflammatory tissues. Therefore, we explored the potential application of 64CuCl2 for PET imaging of inflammation through targeting CTR1. The animal models of H2O2 induced muscle inflammation and lipopolysaccaharide induced lung inflammation were successfully established, then imaged by small animal PET (PET/CT) post-injection of 64CuCl2, and PET images were quantitatively analyzed. H&E and immunohistochemical (IHC) staining and western blot experiments were performed for evaluating CTR1 levels in the inflammatory and control tissues. Both inflammatory muscle and lungs can be clearly imaged by PET. PET image quantitative analysis revealed that the inflammatory muscle and lungs showed significantly higher 64Cu accumulation than the controls, respectively (p < 0.05). Furthermore, IHC staining and western blot analysis demonstrated that compared with the controls, CTR1 expression was increased in both the inflammatory muscle and lungs, which was consistent with the levels of 64Cu2+ accumulation in these tissues. 64CuCl2 can be used as a novel, simple, and highly promising PET tracer for CTR1 targeted imaging of inflammation.

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Research on the Effects of Vitamins and Minerals on Cognitive Function in Older Adults

Best¹,

Dye²

2015

Nutrition for Brain Health and Cognitive Performance

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Copper Status in Alzheimer’s Disease and Other Neurodegenerative Disorders 2013

Cited by 3 publications

References 0 publications

Copper disrupts S-nitrosothiol signaling in activated BV2 microglia

Copper disrupts S-nitrosothiol signaling in activated BV2 microglia

Pilot Study of 64CuCl2 for PET Imaging of Inflammation

Research on the Effects of Vitamins and Minerals on Cognitive Function in Older Adults

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