Tau and Caspase 3 as Targets for Neuroprotection
| Autor: | Regina Ostritsky, Anat Idan-Feldman, Illana Gozes |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Aging
Programmed cell death Article Subject Cognitive Neuroscience Caspase 3 lcsh:Geriatrics Bioinformatics Neuroprotection lcsh:RC321-571 Behavioral Neuroscience Cellular and Molecular Neuroscience mental disorders medicine Viability assay lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Caspase biology Neurodegeneration medicine.disease Cell biology Nap lcsh:RC952-954.6 Neurology Apoptosis biology.protein Neurology (clinical) Research Article |
| Zdroj: | International Journal of Alzheimer's Disease, Vol 2012 (2012) International Journal of Alzheimer's Disease |
| ISSN: | 2090-8024 |
| DOI: | 10.1155/2012/493670 |
| Popis: | The peptide drug candidate NAP (davunetide) has demonstrated protective effects in variousin vivoandin vitromodels of neurodegeneration. NAP was shown to reduce tau hyperphosphorylation as well as to prevent caspase-3 activation and cytochrome-3 release from mitochondria, both characteristic of apoptotic cell death. Recent studies suggest that caspases may play a role in tau pathology. The purpose of this study was to evaluate the effect of NAP on tau hyperphosphorylation and caspase activity in the same biological system. Our experimental setup used primary neuronal cultures subjected to oxygen-glucose deprivation (OGD), with and without NAP or caspase inhibitor. Cell viability was assessed by measuring mitochondrial activity (MTS assay), and immunoblots were used for analyzing protein level. It was shown that apoptosis was responsible for all cell death occurring following ischemia, and NAP treatment showed a concentration-dependent protection from cell death. Ischemia caused an increase in the levels of active caspase-3 and hyperphosphorylated tau, both of which were prevented by either NAP or caspase-inhibitor treatment. Our data suggest that, in this model system, caspase activation may be an upstream event to tau hyperphosphorylation, although additional studies will be required to fully elucidate the cascade of events. |
| Databáze: | OpenAIRE |
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