Affiliations: [a] Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA, USA | [b] Division of Population Science, Fox Chase Cancer Center, Philadelphia, PA, USA
Correspondence:
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Correspondence to: Domenico Praticò, M.D., 706A, MRB, 3420 North Broad Street, Philadelphia, PA 19140, USA. Tel.: +1 215 707 9380; Fax: +1 215 707 7068; E-mail: [email protected].
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-β (Aβ) 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 AβPP Swedish mutant incubated with high levels of homocysteine had an increase in Aβ formation, but no change in Herp level. Finally, over-expression of Herp did not result in any significant modification of Aβ levels. We conclude that the Herp protein pathway is unlikely to be directly involved in the pro-amyloidotic effect of HHcy.
