Regulation of amyloid precursor protein processing by Abeta in human glioma cells
| Autor: | Dan L. Czilli, Christopher Carlson, Bruce D. Gitter |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Aging
Amyloid beta Gene Expression Biology Astrocytoma Neuroprotection Amyloid beta-Protein Precursor mental disorders medicine Amyloid precursor protein Tumor Cells Cultured Humans Secretion RNA Messenger Amyloid beta-Peptides Dose-Response Relationship Drug General Neuroscience Neurotoxicity P3 peptide medicine.disease Peptide Fragments Cell biology medicine.anatomical_structure Biochemistry Astrocytes biology.protein Neuroglia Neurology (clinical) Geriatrics and Gerontology Developmental Biology Astrocyte |
| Zdroj: | Neurobiology of aging. 21(5) |
| ISSN: | 0197-4580 |
| Popis: | Amyloid precursor protein (APP) is cleaved to neurotoxic/proinflammatory amyloid beta protein (Abeta) or to the neuroprotective secreted alpha-APPs. A balance in APP metabolism may influence the outcome between toxicity and protection to central nervous system (CNS) neurons in Alzheimer's disease. Treatment of U-373 MG astrocytoma cells with aggregated Abeta (1-40) decreases APP secretion into the medium to 10-30% of control values. This decreased secretion appears to be specific for APP since Abeta treatment causes an approximately 2-fold increase in interleukin-8 (IL-8) secretion. Abeta treatment also causes a 4- to 9-fold increase in total cell-associated APP. This increase is due to cellular retention of alpha secretase-cleaved APP and a 2-fold increase in mature full-length APP. These data suggest that deposition of aggregated Abeta may contribute to Alzheimer's-associated neurotoxicity by altering the metabolism of the APP protein. Abeta may exert harmful effects by decreasing the secretion of neuroprotective or neurotrophic APP and, in addition, by increasing intracellular full-length APP; thereby providing increased substrate for generation of amyloidogenic peptide within astrocytes. |
| Databáze: | OpenAIRE |
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