Amyloid-β-stimulated plasminogen activation by tissue-type plasminogen activator results in processing of neuroendocrine factors
| Autor: | Albert J. R. Heck, Emile E. Voest, Yoony Y.J. Gent, Martijn F.B.G. Gebbink, Edwin P. Romijn, Onno Kranenburg |
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| Rok vydání: | 2005 |
| Předmět: |
Amyloid
Plasmin Chromaffin Cells Blotting Western Molecular Sequence Data Fluorescent Antibody Technique Peptide Mapping Mice Plasminogen Activators Chromogranins medicine Animals Amino Acid Sequence Fibrinolysin Nerve Growth Factors Cognitive decline Cells Cultured Chromatography High Pressure Liquid Neurons Amyloid beta-Peptides T-plasminogen activator Chemistry General Neuroscience Neuropeptides Neurodegeneration Proteins Plasminogen Long-term potentiation medicine.disease Neurosecretory Systems Mice Inbred C57BL Biochemistry Tissue Plasminogen Activator Plasminogen activator Protein Binding medicine.drug |
| Zdroj: | Neuroscience. 131:877-886 |
| ISSN: | 0306-4522 |
| Popis: | Alzheimer's disease brain is characterized by the abundant presence of amyloid deposits. Accumulation of the major constituent of these deposits, amyloid-beta (Abeta), has been associated with decreased neurotransmission, increased neuronal cell death, and with cognitive decline. The mechanisms underlying these phenomena have not yet been fully elucidated. We have previously shown that amyloid peptides like Abeta bind tissue-type plasminogen activator (tPA) and cause enhanced plasmin production. Here we describe the identification of five major neuronal cell-produced Abeta-associated proteins and how Abeta-stimulated plasmin formation affects their processing. These five proteins are all neuroendocrine factors (NEFs): chromogranins A, B and C; truncated chromogranin B; and VGF. Plasminogen caused processing of Abeta-bound (but not soluble) tPA, chromogranin B and VGF and the degradation products were released from Abeta. Processing of the neuroendocrine factors was dependent on tPA as it was largely abrogated in tPA-/- cells or in the presence of a specific tPA-inhibitor. If plasmin indeed produces NEF-derived peptides in vivo, some of these peptides may have biological activity, for instance in regulating neurotransmitter release that may affect the pathology of Alzheimer's disease. |
| Databáze: | OpenAIRE |
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