Interaction of amyloid binding alcohol dehydrogenase/Abeta mediates up-regulation of peroxiredoxin II in the brains of Alzheimer's disease patients and a transgenic Alzheimer's disease mouse model.
Alzheimer's patients have increased levels of both the 42 beta amyloid-beta-peptide (Abeta) and amyloid binding alcohol dehydrogenase (ABAD) which is an intracellular binding site for Abeta. The over-expression of Abeta and ABAD in transgenic mice has shown that the binding of Abeta to ABAD results in exaggerating neuronal stress and impairment of learning and memory. From a proteomic analysis of the brains from these animals we identified that peroxiredoxin II levels increase in Alzheimer's diseased brain. This increase in peroxiredoxin II levels protects neurons against Abeta induced toxicity. We also demonstrate, for the first time in living animals, that the expression level of peroxiredoxin II is an indicator for the interaction of ABAD and Abeta as its expression levels return to normal if this interaction is perturbed. Therefore this indicates the possibility of reversing changes observed in Alzheimer's disease and that the Abeta-ABAD interaction is a suitable drug target.
Yao
Jun
J
Department of Pathology, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, New York, NY 10032, USA.
Taylor
Margaret
M
Davey
Fleur
F
Ren
Yimin
Y
Aiton
Jim
J
Coote
Peter
P
Fang
Fang
F
Chen
John Xi
JX
Yan
Shi Du
SD
Gunn-Moore
Frank J
FJ
D000426:Alcohol Dehydrogenase / Q000378:metabolism*; D000544:Alzheimer Disease / Q000473:pathology*; D000682:Amyloid / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods; D005786:Gene Expression Regulation; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010544:Peroxidases / Q000378:metabolism*; D054464:Peroxiredoxins; D011485:Protein Binding; D040901:Proteomics / Q000379:methods; D015854:Up-Regulation / Q000502:physiology*
D000682:Amyloid; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D006360:Heat-Shock Proteins; D000426:Alcohol Dehydrogenase; D010544:Peroxidases; C086065:PRDX2 protein, human; D054464:Peroxiredoxins