Zinc Inhibits Amyloid beta Production from Alzheimer's Amyloid Precursor Protein in SH-SY5Y Cells.
10.4196/kjpp.2009.13.3.195
- Author:
Jinu LEE
1
;
Chul Hoon KIM
;
Dong Goo KIM
;
Young Soo AHN
Author Information
1. Department of Pharmacology, School of Medicine, CHA University, Sungnam 463-836, Korea.
- Publication Type:Original Article
- Keywords:
Zinc;
Amyloid beta;
Amyloid precursor protein;
Pyrrolidine dithiocarbamate
- MeSH:
Alzheimer Disease;
Amyloid;
Baths;
Culture Media;
Neurons;
Proline;
Pyrrolidines;
Thiocarbamates;
Zinc
- From:The Korean Journal of Physiology and Pharmacology
2009;13(3):195-200
- CountryRepublic of Korea
- Language:English
-
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 beta40 and A beta42 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 beta40. These results indicate that inhibition of secretase-mediated APP cleavage accounts -at least in part- for zinc inhibition of A beta secretion.
