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The Journal of Biological Chemistry
Year: 2008  |  Volume: 283  |  Issue: 9  |  Page No.: 5685 - 5691

Endophilin I Expression Is Increased in the Brains of Alzheimer Disease Patients

Yimin Ren, Hong Wei Xu, Fleur Davey, Margaret Taylor, Jim Aiton, Peter Coote, Fang Fang, Jun Yao, Doris Chen, John Xi Chen, Shi Du Yan and Frank J. Gunn-Moore    

Abstract: Alzheimer patients have increased levels of both the 42 amyloid-β-peptide (Aβ) and the amyloid binding alcohol dehydrogenase (ABAD), which is an intracellular binding site for Aβ. The overexpression of Aβ and ABAD in transgenic mice has shown that the binding of Aβ 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 Aβ 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.

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