Evidence for excitoprotective and intraneuronal calcium-regulating roles for secreted forms of the beta-amyloid precursor protein
| Autor: | Frederick Esch, Mark P. Mattson, Alan R. Culwell, Bin Cheng, Russell E. Rydel, Ivan Lieberburg |
|---|---|
| Rok vydání: | 1993 |
| Předmět: |
Cell Survival
Glutamic Acid Hippocampal formation Neuroprotection Hippocampus Antibodies Amyloid beta-Protein Precursor Glutamates mental disorders Amyloid precursor protein medicine Animals Humans APLP1 Senile plaques APLP2 Cells Cultured Cerebral Cortex Neurons biology General Neuroscience Glutamate receptor Neurotoxicity medicine.disease Rats Glucose biology.protein Calcium Septum Pellucidum Neuroscience |
| Zdroj: | Neuron. 10(2) |
| ISSN: | 0896-6273 |
| Popis: | The β-amyloid precursor protein (βAPP) is a membrane-spanning glycoprotein that is the source of the β-amyloid peptide (βAP) which accumulates as senile plaques in the brains of patients with Alzheimer's disease. βAPP is normally processed such that a cleavage occurs within the βAP, liberating secreted forms of βAPP (APP s s) from the cell. The neuronal functions of these forms are unknown. We now report that APP s s have a potent neuroprotective action in cultured rat hippocampal and septal neurons and in human cortical neurons. APP s 695 and APP s 751 protected neurons against hypoglycemic damage, and the neuroprotection was abolished by antibodies to a specific region common to both APP s 695 and APP s 751 . APP s s caused a rapid and prolonged reduction in [Ca 2+ ] 1 and prevented the rise in [Ca 2+ ] i that normally mediated hypoglycemic damage. APP s s also protected neurons against glutamate neurotoxicity, effectively raising the excitotoxic threshold. APP s s may normally play excitoprotective and neuromodulatory roles. Alternative processing of APP s s in Alzheimer's disease may contribute to neuronal degeneration by compromising the normal function of APP s s and by promoting the deposition of βAP. |
| Databáze: | OpenAIRE |
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