KMID : 0811720090130030195
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Korean Journal of Physiology & Pharmacology 2009 Volume.13 No. 3 p.195 ~ p.200
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Zinc Inhibits Amyloid ¥â Production from Alzheimer¡¯s Amyloid Precursor Protein in SH-SY5Y Cells
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Lee Jinu
Kim Chul-Hoon Kim Dong-Goo Ahn Young-Soo
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Abstract
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Zinc released from excited glutamatergic neurons accelerates amyloid ¥â (A¥â ) aggregation, underscoring the therapeutic potential of zinc chelation for the treatment of Alzheimer¡¯s disease (AD). Zinc can also alter A¥â concentration by affecting its degradation. In order to elucidate the possible role of zinc influx in secretase-processed A¥â 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¥â40 and A¥â42 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 ¥â- and ¥á-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¥â40. These results indicate that inhibition of secretase-mediated APP cleavage accounts -at least in part- for zinc inhibition of A¥â secretion.
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KEYWORD
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Zinc, Amyloid beta, Amyloid precursor protein, Pyrrolidine dithiocarbamate
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