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International Journal of Alzheimer’s Disease
Volume 2011 (2011), Article ID 985085, 9 pages
http://dx.doi.org/10.4061/2011/985085
Review Article

Targeting Glycogen Synthase Kinase-3β for Therapeutic Benefit against Oxidative Stress in Alzheimer's Disease: Involvement of the Nrf2-ARE Pathway

1Department of Neurobiology, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland
2Department of Pathology, The University of Melbourne, Melbourne, VIC 3010, Australia
3School of Pharmacy, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland
4Department of Oncology, Kuopio University Hospital, P.O. Box 1777, 70211 Kuopio, Finland

Received 29 December 2010; Accepted 1 March 2011

Academic Editor: Peter Crouch

Copyright © 2011 Katja Kanninen 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

Specific regions of the Alzheimer's disease (AD) brain are burdened with extracellular protein deposits, the accumulation of which is concomitant with a complex cascade of overlapping events. Many of these pathological processes produce oxidative stress. Under normal conditions, oxidative stress leads to the activation of defensive gene expression that promotes cell survival. At the forefront of defence is the nuclear factor erythroid 2-related factor 2 (Nrf2), a transcription factor that regulates a broad spectrum of protective genes. Glycogen synthase kinase-3β (GSK-3β) regulates Nrf2, thus making this kinase a potential target for therapeutic intervention aiming to boost the protective activation of Nrf2. This paper aims to review the neuroprotective role of Nrf2 in AD, with special emphasis on the role of GSK-3β in the regulation of the Nrf2 pathway. We also examine the potential of inducing GSK-3β by small-molecule activators, dithiocarbamates, which potentially exert their beneficial therapeutic effects via the activation of the Nrf2 pathway.