Endophilin I expression is increased in the brains of Alzheimer disease patients.
Alzheimer patients have increased levels of both the 42 amyloid-beta-peptide (Abeta) and the amyloid binding alcohol dehydrogenase (ABAD), which is an intracellular binding site for Abeta. The overexpression of Abeta and ABAD in transgenic mice has shown that the binding of Abeta to ABAD results in amplified neuronal stress and impairment of learning and memory. From a proteomic analysis of the brains from these animals, we have identified for the first time that the protein endophilin I increases in Alzheimer diseased brain. The increase in endophilin I levels in neurons is linked to an increase in the activation of the stress kinase c-Jun N-terminal kinase with the subsequent death of the neurons. We also demonstrate in living animals that the expression level of endophilin I is an indicator for the interaction of ABAD and Abeta as its expression levels return to normal if this interaction is perturbed. Therefore this identifies endophilin I as a new indicator of the progression of Alzheimer disease.
Ren
Yimin
Y
Schools of Biology and Medicine, University of St. Andrews, Scotland KY16 9TS.
Xu
Hong Wei
HW
Davey
Fleur
F
Taylor
Margaret
M
Aiton
Jim
J
Coote
Peter
P
Fang
Fang
F
Yao
Jun
J
Chen
Doris
D
Chen
John Xi
JX
Yan
Shi Du
SD
Gunn-Moore
Frank J
FJ
D000217:Acyltransferases / Q000096:biosynthesis* / Q000235:genetics; D000426:Alcohol Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D016923:Cell Death / Q000235:genetics; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D008568:Memory; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D011485:Protein Binding / Q000235:genetics
D016229:Amyloid beta-Peptides; D015415:Biomarkers; D000426:Alcohol Dehydrogenase; D000217:Acyltransferases; C018764:2-acylglycerophosphate acyltransferase; D048031:JNK Mitogen-Activated Protein Kinases