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Role of zinc and copper ions in the pathogenetic mechanisms of Alzheimer’s and Parkinson’s diseases

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Abstract

Disbalance of zinc (Zn2+) and copper (Cu2+) ions in the central nervous system is involved in the pathogenesis of numerous neurodegenerative disorders such as multisystem atrophy, amyotrophic lateral sclerosis, Creutzfeldt-Jakob disease, Wilson-Konovalov disease, Alzheimer’s disease, and Parkinson’s disease. Among these, Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the most frequent age-related neurodegenerative pathologies with disorders in Zn2+ and Cu2+ homeostasis playing a pivotal role in the mechanisms of pathogenesis. In this review we generalized and systematized current literature data concerning this problem. The interactions of Zn2+ and Cu2+ with amyloid precursor protein (APP), β-amyloid (Abeta), tau-protein, metallothioneins, and GSK3β are considered, as well as the role of these interactions in the generation of free radicals in AD and PD. Analysis of the literature suggests that the main factors of AD and PD pathogenesis (oxidative stress, structural disorders and aggregation of proteins, mitochondrial dysfunction, energy deficiency) that initiate a cascade of events resulting finally in the dysfunction of neuronal networks are mediated by the disbalance of Zn2+ and Cu2+.

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Abbreviations

Abeta:

β-amyloid

AD:

Alzheimer’s disease

APP:

amyloid precursor protein

ASN:

alpha-synuclein

GABA:

γ-aminobutyric acid

GSK3β:

glycogen synthase kinase 3β

MPP(+):

1-methyl-4-phenylpyridine

MPTP:

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

NMDA:

N-methyl-D-aspartate

6-OHDA:

6-hydroxydopamine

PD:

Parkinson’s disease

ROS:

reactive oxygen species

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Authors and Affiliations

  1. Research Center of Neurology, Russian Academy of Medical Sciences, Volokolamskoe Shosse 80, 125367, Moscow, Russia

    E. V. Stelmashook, N. K. Isaev, E. E. Genrikhs, L. G. Khaspekov, V. G. Skrebitsky & S. N. Illarioshkin

  2. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992, Moscow, Russia

    N. K. Isaev & G. A. Amelkina

Authors
  1. E. V. Stelmashook
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  2. N. K. Isaev
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  3. E. E. Genrikhs
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  4. G. A. Amelkina
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  5. L. G. Khaspekov
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Correspondence to E. V. Stelmashook.

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Original Russian Text © E. V. Stelmashook, N. K. Isaev, E. E. Genrikhs, G. A. Amelkina, L. G. Khaspekov, V. G. Skrebitsky, S. N. Illarioshkin, 2014, published in Biokhimiya, 2014, Vol. 79, No. 5, pp. 501–508.

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Stelmashook, E.V., Isaev, N.K., Genrikhs, E.E. et al. Role of zinc and copper ions in the pathogenetic mechanisms of Alzheimer’s and Parkinson’s diseases. Biochemistry Moscow 79, 391–396 (2014). https://doi.org/10.1134/S0006297914050022

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