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Role of Interaction between Zinc and Amyloid Beta in Pathogenesis of Alzheimer’s Disease

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Abstract

Progression of Alzheimer’s disease is accompanied by the appearance of extracellular deposits in the brain tissues of patients with characteristic supramolecular morphology (amyloid plaques) the main components of which are β-amyloid isoforms (Aβ) and biometal ions (zinc, copper, iron). For nearly 40 years and up to the present time, the vast majority of experimental data indicate critical role of formation and accumulation of amyloid plaques (cerebral amyloidogenesis) in pathogenesis of Alzheimer’s disease, however, nature of the molecular agents that initiate cerebral amyloidogenesis, as well as causes of aggregation of the native Aβ molecules in vivo remained unknown for a long time. This review discusses the current level of fundamental knowledge about the molecular mechanisms of interactions of zinc ions with a number of Aβ isoforms present in amyloid plaques of the patients with Alzheimer’s disease, and also shows how this knowledge made it possible to identify driving forces of the cerebral amyloidogenesis in Alzheimer’s disease and made it possible to determine fundamentally new biomarkers and drug targets as part of development of innovative strategy for diagnosis and treatment of Alzheimer’s disease.

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Abbreviations

Aβ:

amyloid beta

Aβ(i-j):

a continuous linear fragment starting from i-th position to j-th position of the human Aβ amino acid sequence, 1DAEFRHDSGYEVHHQKLVFFAEDVGSNKGAIIGLMVGGVVIA42 (single-letter amino acid code)

AD:

Alzheimer’s disease

CA:

cerebral amyloidogenesis in Alzheimer’s disease

HAEE:

tetrapeptide acetyl-HAEE-NH2

isoD7:

isomerized D7

isoD7-Aβ:

isoD7-bearing amyloid beta

NMR:

nuclear magnetic resonance

pS8:

phosphorylated serine residue at S8

pS8-Aβ:

pS8-bearing amyloid beta

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Funding

The study was financially supported by the Russian Science Foundation (grant no. 19-74-30007).

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  1. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991, Moscow, Russia

    Sergey A. Kozin

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  1. Sergey A. Kozin
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Correspondence to Sergey A. Kozin.

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The author declares no conflicts of interest in financial or any other sphere. This article does not contain any studies with human participants or animals performed by any of the authors.

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Translated from Uspekhi Biologicheskoi Khimii, 2023, Vol. 63, pp. 149-174.

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Kozin, S.A. Role of Interaction between Zinc and Amyloid Beta in Pathogenesis of Alzheimer’s Disease. Biochemistry Moscow 88 (Suppl 1), S75–S87 (2023). https://doi.org/10.1134/S0006297923140055

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