The Herp protein pathway is not involved in the pro-amyloidogenic effect of hyperhomocysteinemia.
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 (Abeta) 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 AbetaPP Swedish mutant incubated with high levels of homocysteine had an increase in Abeta formation, but no change in Herp level. Finally, over-expression of Herp did not result in any significant modification of Abeta levels. We conclude that the Herp protein pathway is unlikely to be directly involved in the pro-amyloidotic effect of HHcy.
Zhuo
Jia-Min
JM
Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA, USA.
Kruger
Warren D
WD
Praticò
Domenico
D
D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D002461:Cell Line, Transformed; D006224:Cricetinae; D003412:Cricetulus; D003541:Cystathionine beta-Synthase / Q000172:deficiency; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D020138:Hyperhomocysteinemia / Q000235:genetics* / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; C485932:HERPUD1 protein, human; D008565:Membrane Proteins; D003541:Cystathionine beta-Synthase