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Link Between Metal Homeostasis and Neurodegenerative Diseases: Crosstalk of Metals and Amyloidogenic Proteins at the Synapse

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Metallomics

Abstract

Increasing evidence suggests that disruption of metal homeostasis contributes to the pathogenesis of various neurodegenerative diseases, including Alzheimer’s disease, Lewy body diseases, vascular dementia, and prion diseases. Conformational changes of disease-related proteins such as ß-amyloid protein, α-synuclein, and prion proteins are well-established contributors to the synaptotoxicity, neurotoxicity, and pathogenesis of these diseases. Recent studies have revealed that these proteins are metalloproteins that coexist in synapses and play significant roles in the maintenance of metal homeostasis in synapses. Trace elements such as zinc (Zn), iron (Fe), copper (Cu), and aluminum (Al) bind to these proteins, thereby influencing their conformations and functions. Additionally, these metals have common binding sites; binding of metals to proteins is nonspecific. Therefore, metal-metal interactions at synapses contribute to the neurodegenerative processes. We present a current review of the role of trace elements in the functions and toxicity of disease-related proteins, as well as in the pathogenesis of neurodegenerative diseases. Possible therapeutic approaches related to metal homeostasis are discussed.

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Authors and Affiliations

  1. Department of Forensic Medicine, Faculty of Medicine, Yamagata University, 2-2-2 Iida-Nishi, Yamagata-shi, Yamagata, 990-9585, Japan

    Dai Mizuno

  2. Department of Bio-Analytical Chemistry, Faculty of Pharmacy, Musashino University, Nishi-Tokyo shi, Tokyo, 202-8585, Japan

    Masahiro Kawahara Ph.D.

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Correspondence to Masahiro Kawahara Ph.D. .

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  1. Graduate School of Pharmaceutical Science, Chiba University, Chiba, Japan

    Yasumitsu Ogra

  2. Graduate School of Science, The University of Tokyo, Tokyo, Japan

    Takafumi Hirata

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Mizuno, D., Kawahara, M. (2017). Link Between Metal Homeostasis and Neurodegenerative Diseases: Crosstalk of Metals and Amyloidogenic Proteins at the Synapse. In: Ogra, Y., Hirata, T. (eds) Metallomics. Springer, Tokyo. https://doi.org/10.1007/978-4-431-56463-8_14

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