Affiliations: [a] Department of Preventive Medicine & Community Health, University of Texas Medical Branch, Galveston, TX 77555, USA | [b] Department of Preventive Medicine & Community Health and Anesthesiology, University of Texas Medical Branch, Galveston, TX 77555, USA
Correspondence:
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Corresponding author: Wolfgang Maret, Ph.D., Division of Human Nutrition, Preventive Medicine and Community Health, University of Texas Medical Branch, 700 Harborside Drive, Galveston, TX 77555, USA. Tel.: +1 409 772 4661; Fax: +1 409 772 6287; E-mail: womaret@utmb.edu.
Abstract: Alzheimer's disease is associated with oxidative stress and changes in metal metabolism. Among the essential trace metals, zinc has the greatest number and variety of functions in hundreds of enzymes and thousands of protein domains with different types of zinc finger motifs. Moreover, zinc ions are stored in synaptic vesicles of specialized neurons and released during neuronal activity. Based on this multitude of functions, one would expect that impairment of zinc homeostasis in the brain has far-reaching consequences. In spite of the fact that zinc ions are redox-inert in biology, they have profound effects on redox metabolism. Thus, both zinc deficiency and zinc overload elicit oxidative stress that can lead to the death of nerve cells. These pro-oxidant functions contrast with pro-antioxidant functions in a range of physiological zinc concentrations. Oxidative or nitrosative stress can release zinc from proteins with zinc finger and cluster motifs and re-distribute zinc, thereby changing the functions of the proteins from which it is released and to which it binds. The transduction of redox signals into zinc signals and vice versa affects mitochondrial functions and signaling pathways (NF-κB, p53, AP-1) where zinc and the zinc donor/acceptor pair metallothionein/thionein are critically involved in life and death decisions of the cell.
