Role of Copper Dyshomeostasis in the Pathogenesis of Parkinson’s Disease

Karpenko, Marina N.; Ilyicheva, E. Yu.; Muruzheva, Zamira M.; Milyukhina, I. V.; Orlov, Yury; Puchkova, L. V.

doi:10.1007/s10517-018-4039-4

Cited by 12 publications

(5 citation statements)

References 10 publications

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“…Copper dyshomeostasis, manifested as an alteration of copper status indices, is not a mandatory feature of PD. Previously, we screened a cohort of 50 PD patients and only revealed 17 patients with copper status indices that were characteristic of heterozygous WD carriers [83], but our experience still indicates that copper status observation in PD patients is sensible. The timely detection of a heterozygous WD gene in patients with PD clinical symptoms and the prescription of chelation therapy may help to slow down or even prevent PD development.…”

Section: Discussionmentioning

confidence: 99%

Case of Early-Onset Parkinson’s Disease in a Heterozygous Mutation Carrier of the ATP7B Gene

Ilyechova

Miliukhina

Karpenko

et al. 2019

JPM

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In this paper, we report a clinically proven case of Parkinson’s disease (PD) with early onset in a patient who is a heterozygous mutation carrier of ATP7B (the Wilson’s disease gene). The patient was observed from 2011 to 2018 in the Center for Neurodegenerative Diseases, Institute of Experimental Medicine (St. Petersburg, Russia). During this period, the patient displayed aggravation of PD clinical symptoms that were accompanied by a decrease in the ceruloplasmin concentration (from 0.33 to 0.27 g/L) and an increase in serum nonceruloplasmin copper, which are typical of the late stages of Wilson’s disease. It was found that one of the alleles of exon 14 in the ATP7B gene, which partially codes of the nucleotide-binding domain (N-domain), carries a mutation not previously reported corresponding to Cys1079Gly substitution. Alignment of the ATP7B N-domain amino acid sequences of representative vertebrate species has shown that the Cys at 1079 position is conserved throughout the evolution. Molecular dynamic analysis of a polypeptide with Cys1079Gly substitution showed that the mutation causes profound conformational changes in the N-domain, which could potentially lead to impairment of its functions. The role of ATP7B gene mutations in PD development is discussed.

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Section: Discussionmentioning

confidence: 99%

Case of Early-Onset Parkinson’s Disease in a Heterozygous Mutation Carrier of the ATP7B Gene

Ilyechova

Miliukhina

Karpenko

et al. 2019

JPM

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“…Thus, albumin takes part in the transport of copper [ 112 ]. Copper is a cofactor of many enzymes and a participant in redox reactions and signaling pathways in the body in normal and pathological states [ 113 ]. The main binding site of Cu(II) cations is the N-terminal site (NTS) of HSA Asp-Ala-His-Lys [ 114 ].…”

Section: Redox Modulation and Redox Activity Of Albuminmentioning

confidence: 99%

Serum Albumin in Health and Disease: Esterase, Antioxidant, Transporting and Signaling Properties

Belinskaia

Voronina

Шмурак

et al. 2021

IJMS

138

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Being one of the main proteins in the human body and many animal species, albumin plays a decisive role in the transport of various ions—electrically neutral and charged molecules—and in maintaining the colloidal osmotic pressure of the blood. Albumin is able to bind to almost all known drugs, as well as many nutraceuticals and toxic substances, largely determining their pharmaco- and toxicokinetics. Albumin of humans and respective representatives in cattle and rodents have their own structural features that determine species differences in functional properties. However, albumin is not only passive, but also an active participant of pharmacokinetic and toxicokinetic processes, possessing a number of enzymatic activities. Numerous experiments have shown esterase or pseudoesterase activity of albumin towards a number of endogeneous and exogeneous esters. Due to the free thiol group of Cys34, albumin can serve as a trap for reactive oxygen and nitrogen species, thus participating in redox processes. Glycated albumin makes a significant contribution to the pathogenesis of diabetes and other diseases. The interaction of albumin with blood cells, blood vessels and tissue cells outside the vascular bed is of great importance. Interactions with endothelial glycocalyx and vascular endothelial cells largely determine the integrative role of albumin. This review considers the esterase, antioxidant, transporting and signaling properties of albumin, as well as its structural and functional modifications and their significance in the pathogenesis of certain diseases.

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“…The potentiation between copper and iron in Parkinson disease patients was proved in cerebrospinal fl uid as well (104). Another study reported that number of copper ions bound on one molecule of ceruloplasmin was reduced in patients suffering from Parkinson disease (105). Using a model comprising laboratory rats, symptoms of Parkinson disease and damaging of the pars compacta of substantia nigra was initiated by administered copper (106).…”

Section: Alzheimer Disease and The Other Neurodegenerationsmentioning

confidence: 98%

Copper and copper nanoparticles toxicity and their impact on basic functions in the body

Pohanka¹

2019

BLL

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Copper is a biogenic metal having multiple functions in basic processes in organisms and it is common in all kingdoms of life. Limited intake of copper is a problem; however, doses of copper exceeding the recommended alimentary source are problematic as well and toxicity is soon manifested. Impact of copper nanoparticles on human health is another serious issue taken into consideration in this review. Regarding to copper toxicity, neurodegenerative disorders including Alzheimer and Parkinson diseases are suspected to be linked to copper toxicity or copper can contribute to their progression. Wilson and Menke diseases are also described as examples of copper intolerance. This paper is focused on the description, literature survey and discussion of the current knowledge about copper and copper nanoparticles toxicity and their involvement in various pathological processes (Tab. 6, Fig. 2, Ref. 171).

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Role of Copper Dyshomeostasis in the Pathogenesis of Parkinson’s Disease

Cited by 12 publications

References 10 publications

Case of Early-Onset Parkinson’s Disease in a Heterozygous Mutation Carrier of the ATP7B Gene

Case of Early-Onset Parkinson’s Disease in a Heterozygous Mutation Carrier of the ATP7B Gene

Serum Albumin in Health and Disease: Esterase, Antioxidant, Transporting and Signaling Properties

Copper and copper nanoparticles toxicity and their impact on basic functions in the body

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