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Endophilin I Expression Is Increased in the Brains of Alzheimer Disease Patients
- Source :
- Journal of Biological Chemistry. 283:5685-5691
- Publication Year :
- 2008
- Publisher :
- Elsevier BV, 2008.
-
Abstract
- 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.
- Subjects :
- Genetically modified mouse
medicine.medical_specialty
Amyloid
Transgene
Mice, Transgenic
Biology
Biochemistry
Mice
Alzheimer Disease
Memory
Internal medicine
medicine
Animals
Humans
Binding site
Molecular Biology
Alcohol dehydrogenase
Neurons
Amyloid beta-Peptides
Cell Death
Kinase
Alcohol Dehydrogenase
JNK Mitogen-Activated Protein Kinases
Brain
Cell Biology
medicine.disease
Endocrinology
biology.protein
Alzheimer's disease
Acyltransferases
Biomarkers
Intracellular
Protein Binding
Subjects
Details
- ISSN :
- 00219258
- Volume :
- 283
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Chemistry
- Accession number :
- edsair.doi.dedup.....8b8d68c93b007d87548a8d113967d630