REVIEW: Role of Zinc and Copper Ions in the Pathogenetic Mechanisms of Alzheimer’s and Parkinson’s Diseases

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E. V. Stelmashook^1*, N. K. Isaev^1,2, E. E. Genrikhs¹, G. A. Amelkina², L. G. Khaspekov¹, V. G. Skrebitsky¹, and S. N. Illarioshkin¹

¹Research Center of Neurology, Russian Academy of Medical Sciences, Volokolamskoe Shosse 80, 125367 Moscow, Russia; fax: (495) 490-2210; E-mail: estelmash@mail.ru

²Lomonosov Moscow State University, Belozersky Institute of Physico-Chemical Biology, 119992 Moscow, Russia; fax: (495) 939-3181; E-mail: isaev@genebee.msu.ru

^* To whom correspondence should be addressed.

Received October 7, 2013; Revision received January 21, 2014

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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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KEY WORDS: zinc ions, copper ions, Alzheimer’s disease, Parkinson’s disease, mitochondria-targeted antioxidants

DOI: 10.1134/S0006297914050022

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