Increased Expression of the Remodeling- and Tumorigenic-Associated Factor Osteopontin in Pyramidal Neurons of the Alzheimers Disease Brain
| Autor: | Glenda M. Bishop, David T. Denhardt, John Wung, Peggy L.R. Harris, Craig S. Atwood, Mehul A. Trivedi, Aaron J. Kowalski, Sterling C. Johnson, Mark A. Smith, George Perry |
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| Rok vydání: | 2007 |
| Předmět: |
Male
Cell type Pathology medicine.medical_specialty Neurite Cell Count Biology stomatognathic system Alzheimer Disease medicine Humans Osteopontin Remyelination Aged Aged 80 and over Pyramidal Cells Neurodegeneration Cell migration Middle Aged Cell cycle medicine.disease Immunohistochemistry medicine.anatomical_structure Gene Expression Regulation Neurology Case-Control Studies biology.protein Cancer research Female Neurology (clinical) Neuron |
| Zdroj: | Current Alzheimer Research. 4:67-72 |
| ISSN: | 1567-2050 |
| DOI: | 10.2174/156720507779939869 |
| Popis: | Osteopontin (OPN) is a glycophosphoprotein expressed by several cell types and has pro-adhesive, chemotactic, and cytokine-like properties. OPN is involved in a number of physiologic and pathologic events including angiogenesis, apoptosis, inflammation, oxidative stress, remyelination, wound healing, bone remodeling, cell migration and tumorigenesis. Since these functions of OPN, and the events that it regulates, are involved with neurodegeneration, we examined whether OPN was differentially expressed in the hippocampus of the Alzheimer's disease (AD) compared with age-matched (59-93 years) control brain. We report for the first time the immunocytochemical localization of OPN in the cytoplasm of pyramidal neurons. In AD brains, there was a significant 41 % increase in the expression of neuron OPN compared with age-matched control brain. No staining of other neuronal cell types was observed. Additionally, there was a significant positive correlation between OPN staining intensity and both amyloid-beta load (r(2) = 0.25; P < 0.05; n = 20) and aging (r(2) = 0.32; P < 0.01; n = 20) among all control and AD subjects. Controlling for age indicated that OPN expression was significantly influenced by amyloid-beta load, but not age. While the functional consequences of this amyloid-beta associated increase in OPN expression are unclear, it is notable that OPN is primarily localized to those neurons that are known to be vulnerable to AD-related neurite loss, degeneration and death. Given that the induction of OPN expression (and amyloid-beta generation) is associated with remodeling and tumorigenesis, our results suggest that OPN may play a role in the aberrant re-entry of neurons into the cell cycle and/or neuronal remyelination in AD. |
| Databáze: | OpenAIRE |
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