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Zhuo JM , Kruger WD , Pratico D
The Herp Protein Pathway is Not Involved in the Pro-Amyloidogenic Effect of Hyperhomocysteinemia
Journal of Alzheimers Disease. 2010 ;20(2) :569-576
PMID: ISI:000279537700021   
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Abstract
Diet-induced high circulating levels of homocysteine, also known as hyper-homocysteinemia (HHcy), is associated with an acceleration of Alzheimer's disease-like amyloidosis. Herp is a homocysteine-responsive stress protein, which has been shown to increase the formation of amyloid-beta (A beta) via interaction with presenilins in vitro. The aim of our paper was to investigate the functional role that Herp plays in HHcy-induced amyloidosis. Amyloidosis secondary to diet-induced HHcy in Tg2576 mice is associated with an increase of Herp protein and mRNA levels. By contrast, no other stress-related proteins are altered by the same diet regimen. Compared to wild type animals, brains from a genetically induced HHcy mouse model did not manifest any significant change in Herp levels. Cells stably over-expressing human A beta PP Swedish mutant incubated with high levels of homocysteine had an increase in A beta formation, but no change in Herp level. Finally, over-expression of Herp did not result in any significant modification of A beta levels. We conclude that the Herp protein pathway is unlikely to be directly involved in the pro-amyloidotic effect of HHcy.
Notes
Zhuo, Jia-Min Kruger, Warren D. Pratico, Domenico National Institute of Health [AG-22512, HLBI16327]; Alzheimer's Association This work was funded by grants from the National Institute of Health, AG-22512 (D.P.), HLBI16327 (W.D.K.), and the Alzheimer's Association (D.P.). We thank Dr. Linda M. Hendershot (St. Jude Children's Research Hospital, Memphis, TN, USA) for providing Herp plasmid. We also appreciate the support of Pennsylvania Commonwealth to the Fox Chase Cancer Center. 25 Ios press; nieuwe hemweg 6b, 1013 bg amsterdam, netherlands 620xy