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The influx of extracellular Zn2+ is used for memory via cognitive activity and is regulated for synaptic plasticity, a cellular mechanism of memory. When Zn2+ influx into neurons excessively occurs, however, it becomes a critical trigger for cognitive decline and neurodegeneration, resulting in acute and chronic pathogenesis. Aging, a biological process, generally accelerates vulnerability to neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD). The basal level of extracellular Zn2+ is age relatedly increased in the rat hippocampus, and the influx of extracellular Zn2+ contributes to accelerating vulnerability to the AD and PD pathogenesis in experimental animals with aging. Metallothioneins (MTs) are Zn2+-binding proteins for cellular Zn2+ homeostasis and involved in not only supplying functional Zn2+ required for cognitive activity, but also capturing excess (toxic) Zn2+ involved in cognitive decline and neurodegeneration. Therefore, it is estimated that regulation of MT synthesis is involved in both neuronal activity and neuroprotection. The present report provides recent knowledge regarding the protective\/preventive potential of MT synthesis against not only normal aging but also the AD and PD pathogenesis in experimental animals, focused on MT function in bidirectional Zn2+ signaling in synaptic dynamics.<\/jats:p>","DOI":"10.1093\/mtomcs\/mfae039","type":"journal-article","created":{"date-parts":[[2024,9,1]],"date-time":"2024-09-01T14:47:17Z","timestamp":1725202037000},"source":"Crossref","is-referenced-by-count":7,"title":["Insight into brain metallothioneins from bidirectional Zn2+ signaling in synaptic dynamics"],"prefix":"10.1093","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7519-2957","authenticated-orcid":false,"given":"Atsushi","family":"Takeda","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences , , 52-1 Yada, Suruga-ku, Shizuoka 422-8526 , Japan"},{"name":"University of Shizuoka , , 52-1 Yada, Suruga-ku, Shizuoka 422-8526 , Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haruna","family":"Tamano","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences , , 52-1 Yada, Suruga-ku, Shizuoka 422-8526 , Japan"},{"name":"University of Shizuoka , , 52-1 Yada, Suruga-ku, Shizuoka 422-8526 , Japan"},{"name":"Shizuoka Tohto Medical College, 1949 Minamiema, Izunokuni , Shizuoka 410-2221 , Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2024,9,2]]},"reference":[{"issue":"1","key":"2024091913093513300_bib1","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1113\/jphysiol.1988.sp017223","article-title":"Brain fluid calcium concentration and response to acute hypercalcaemia during development in the rat","volume":"402","author":"Jones","year":"1988","journal-title":"J. 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