Brain Prolyl Endopeptidase Expression in Aging, APP Transgenic Mice and Alzheimer’s Disease
| Autor: | Steffen Roßner, Hans-Ulrich Demuth, Ulrike Zeitschel, Reinhard Schliebs, Ingo Schulz, Volker Bigl |
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| Rok vydání: | 2005 |
| Předmět: |
Genetically modified mouse
Aging medicine.medical_specialty Cerebellum Transgene education Neuropeptide Mice Transgenic Biology Hippocampal formation Biochemistry Amyloid beta-Protein Precursor Mice Cellular and Molecular Neuroscience Prolyl endopeptidase Alzheimer Disease Internal medicine medicine Extracellular Animals Humans Serine Endopeptidases Brain General Medicine Subcellular localization Endocrinology medicine.anatomical_structure cardiovascular system Prolyl Oligopeptidases circulatory and respiratory physiology medicine.drug |
| Zdroj: | Neurochemical Research. 30:695-702 |
| ISSN: | 1573-6903 0364-3190 |
| Popis: | Prolyl endopeptidase (PEP) is believed to inactivate neuropeptides that are present in the extracellular space. However, the intracellular localization of PEP suggests additional, yet unidentified physiological functions for this enzyme. Here we studied the expression, enzymatic activity and subcellular localization of PEP in adult and aged mouse brain as well as in brains of age-matched APP transgenic Tg2576 mice and in brains of Alzheimer's disease patients. In mouse brain PEP was exclusively expressed by neurons and displayed region- and age-specific differences in expression levels, with the highest PEP activity being present in cerebellum and a significant increase in hippocampal but not cortical or cerebellar PEP activity in aged mouse brain. In brains of young APP transgenic Tg2576 mice, hippocampal PEP activity was increased compared to wild-type littermates in the pre-plaque phase but not in aged mice with beta-amyloid plaque pathology. This "accelerated aging" with regard to hippocampal PEP expression in young APP transgenic mice might be one factor contributing to the observed cognitive deficits in these mice in the pre-plaque phase and could also explain in part the cognition-enhancing effects of PEP inhibitors in several experimental paradigms. |
| Databáze: | OpenAIRE |
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