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GSK-3b-Nrf2 Signaling Pathway as a Neuroprotective Mechanism in Alzheimer’s Disease

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Author(s)
LEE Chan, JANG Jung-Hee
Keimyung Author(s)
Jang, Jung Hee
Department
Dept. of Pharmacology (약리학)
Journal Title
대한약학회 춘계총회 및 학술대회
Issued Date
2010
Abstract
β-Amyloid peptide (Aβ) is the major component of senile plaques
accumulated in the brains of patients with Alzheimer’s disease (AD)
and has been reported to cause neuronal cell death via oxidative stress.
Therefore, attention has been focused on identifying redox-sensitive
transcription factors and their target genes protecting against Aβ-
induced oxidative cell death. Nrf2 plays a pivotal role in the
transcriptional regulation of antioxidant proteins and detoxification
enzymes and blocks apoptosis caused by a wide array of death signals.
Ectopic expression of Nrf2 rescued cells from Aβ-induced cytotoxicity,
apoptosis, intracellular accumulation of reactive oxygen species and
oxidative damages. Moreover, Nrf2 overexpression increased the
expression of γ-glutamylcysteine ligase (GCL), a rate-limiting enzyme
in cellular glutathione biosynthesis and heme oxygenase-1 (HO-1), a
key enzyme in heme degradation process. Conversely, knockdown of
Nrf2 gene expression with siRNA or dominant negative mutant Nrf2
exacerbated Aβ-induced oxidative cell death. To further elucidate the
upstream regulator for Nrf2 activation, we have focused on glycogen
synthase kinase-3β (GSK-3β). Inhibition of Ab-induced GSK-3β
activation by pharmacological inhibitors such as LiCl led to nuclear
accumulation Nrf2 and transcriptional activation of Nrf2 downstream
target genes and protected against Aβ-mediated oxidative cell death. In
another experiment, some dietary and medicinal phytochemicals
attenuated Aβ-induced oxidative cell death via suppression of GSK-3β
and subsequent activation of Nrf2. Taken together, these findings
suggest that GSK-3β-Nrf2 signaling pathway may act as a survival
mediator against AD.
Keimyung Author(s)(Kor)
장정희
Publisher
School of Medicine (의과대학)
Citation
LEE Chan, JANG Jung-Hee. (2010). GSK-3b-Nrf2 Signaling Pathway as a Neuroprotective Mechanism in Alzheimer’s Disease. 대한약학회 춘계총회 및 학술대회, 212–212.
Type
Article
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/41267
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Pharmacology (약리학)
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