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Zinc Inhibits Amyloid ${\beta}$ Production from Alzheimer's Amyloid Precursor Protein in SH-SY5Y Cells  

Lee, Jin-U (Department of Pharmacology, School of Medicine, CHA University)
Kim, Chul-Hoon (Department of Pharmacology, Brain Research Institute, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine)
Kim, Dong-Goo (Department of Pharmacology, Brain Research Institute, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine)
Ahn, Young-Soo (Department of Pharmacology, Brain Research Institute, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine)
Publication Information
The Korean Journal of Physiology and Pharmacology / v.13, no.3, 2009 , pp. 195-200 More about this Journal
Abstract
Zinc released from excited glutamatergic neurons accelerates amyloid ${\beta}$ (A ${\beta}$) aggregation, underscoring the therapeutic potential of zinc chelation for the treatment of Alzheimer's disease (AD). Zinc can also alter A ${\beta}$ concentration by affecting its degradation. In order to elucidate the possible role of zinc influx in secretase-processed A ${\beta}$ production, SH-SY5Y cells stably expressing amyloid precursor protein (APP) were treated with pyrrolidine dithiocarbamate (PDTC), a zinc ionophore, and the resultant changes in APP processing were examined. PDTC decreased A ${\beta}$ 40 and A ${\beta}$ 42 concentrations in culture media bathing APP-expressing SH-SY5Y cells. Measuring the levels of a series of C-terminal APP fragments generated by enzymatic cutting at different APP-cleavage sites showed that both ${\beta}$-and ${\alpha}$-cleavage of APP were inhibited by zinc influx. PDTC also interfered with the maturation of APP. PDTC, however, paradoxically increased the intracellular levels of A ${\beta}$ 40. These results indicate that inhibition of secretase-mediated APP cleavage accounts -at least in part- for zinc inhibition of A ${\beta}$ secretion.
Keywords
Zinc; Amyloid beta; Amyloid precursor protein; Pyrrolidine dithiocarbamate;
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