Brain Function and Pathophysiology Focused on Zn<sup>2+</sup> Dynamics

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  • 亜鉛イオン動態を機軸とする脳の機能と病態解析
  • アエン イオン ドウタイ オ キジク ト スル ノウ ノ キノウ ト ビョウタイ カイセキ

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Abstract

<p>The basal levels of intracellular Zn2+ and extracellular Zn2+ are in the range of ～100 pM and ～10 nM, respectively, in the brain. Extracellular Zn2+ dynamics is involved in both cognitive performance and neurodegeneration. The bidirectional actions are linked with extracellular glutamate and amyloid-β1-42 (Aβ1-42). Intracellular Zn2+ signaling via extracellular glutamate is required for learning and memory, while intracellular Zn2+ dysregulation induces cognitive decline. Furthermore, human Aβ1-42, a causative peptide in Alzheimer's disease pathogenesis captures extracellular Zn2+ and readily taken up into hippocampal neurons followed by intracellular Zn2+ dysregulation. Aβ1-42-mediated intracellular Zn2+ dysregulation is accelerated with aging, because extracellular Zn2+ is age-relatedly increased, resulting in Aβ1-42-induced cognitive decline and neurodegeneration with aging. On the other hand, metallothioneins, zinc-binding proteins can capture Zn2+ released from intracellular Zn-Aβ1-42 complexes and serve for intracellular Zn2+-buffering to maintain intracellular Zn2+ homeostasis. This review summarizes Zn2+ function and its neurotoxicity in the brain, and also the potential defense strategy via metallothioneins against Aβ1-42-induced pathogenesis.</p>

Journal

  • YAKUGAKU ZASSHI

    YAKUGAKU ZASSHI 142 (8), 855-866, 2022-08-01

    The Pharmaceutical Society of Japan

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