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International Journal of Alzheimer’s Disease
Volume 2012 (2012), Article ID 493670, 8 pages
http://dx.doi.org/10.1155/2012/493670
Research Article

Tau and Caspase 3 as Targets for Neuroprotection

The Adams Super Center for Brain Studies, The Lily and Avraham Gildor Chair for The Investigation of Growth Factors, The Elton Laboratory for Molecular Neuroendocrinology, and Department of Human Molecular Genetics and Biochemistry, Sagol School of Neuroscience, Sackler Faculty of Medicine, Tel Aviv University, 69978 Tel Aviv, Israel

Received 27 February 2012; Accepted 1 April 2012

Academic Editor: Hanna Rosenmann

Copyright © 2012 Anat Idan-Feldman et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The peptide drug candidate NAP (davunetide) has demonstrated protective effects in various in vivo and in vitro models 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.