Caspase-2 mediates neuronal cell death induced by beta-amyloid
| Autor: | Wilma J. Friedman, Michael L. Shelanski, Thierry Frappier, Carol M. Troy, Sylvia A. Rabacchi, Kristy A. Brown |
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| Rok vydání: | 2000 |
| Předmět: |
Programmed cell death
Sympathetic Nervous System Caspase 2 Models Neurological Caspase 3 Apoptosis Hippocampus PC12 Cells Nitric oxide Oligodeoxyribonucleotides Antisense chemistry.chemical_compound Mice mental disorders Animals Nerve Growth Factors ARTICLE Caspase Cells Cultured Mice Knockout Neurons Amyloid beta-Peptides Nitrates biology Superoxide Dismutase General Neuroscience Embryo Mammalian Molecular biology Peptide Fragments Rats Nitric oxide synthase chemistry Caspases biology.protein Peroxynitrite |
| Zdroj: | The Journal of neuroscience : the official journal of the Society for Neuroscience. 20(4) |
| ISSN: | 0270-6474 |
| Popis: | β-amyloid (Aβ) has been proposed to play a role in the pathogenesis of Alzheimer's disease (AD). Deposits of insoluble Aβ are found in the brains of patients with AD and are one of the pathological hallmarks of the disease. It has been proposed that Aβ induces death by oxidative stress, possibly through the generation of peroxynitrite from superoxide and nitric oxide. In our current study, treatment with nitric oxide generators protected against Aβ-induced death, whereas inhibition of nitric oxide synthase afforded no protection, suggesting that formation of peroxynitrite is not critical for Aβ-mediated death. Previous studies have shown that aggregated Aβ can induce caspase-dependent apoptosis in cultured neurons. In all of the neuronal populations studied here (hippocampal neurons, sympathetic neurons, and PC12 cells), cell death was blocked by the broad spectrum caspase inhibitorN-benzyloxycarbonyl-val-ala-asp-fluoromethyl ketone and more specifically by the downregulation of caspase-2 with antisense oligonucleotides. In contrast, downregulation of caspase-1 or caspase-3 did not block Aβ1–42-induced death. Neurons from caspase-2 null mice were totally resistant to Aβ1–42toxicity, confirming the importance of this caspase in Aβ-induced death. The results indicate that caspase-2 is necessary for Aβ1–42-induced apoptosisin vitro. |
| Databáze: | OpenAIRE |
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