Affiliations: [a] Department of Neurology, The Affiliated Hospital of Guangdong Medical College, Zhanjiang, China | [b] Department of Urology, The University of Kansas Medical Center, Kansas City, KS, USA
Correspondence:
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Correspondence to: Bin Zhao, Department of Neurology, The Affiliated Hospital of Guangdong Medical College, No. 2 Wenming Donglu, Xiashan District, Zhanjiang, Guangdong Province, People's Republic of China. Tel.: 86 759 2388505; Fax: 86 759 2284104; E-mail: zhaobin0759@gmail.com.
Abstract: Glycogen synthase kinase 3β (GSK-3β) plays a critical role in the pathogenesis of Alzheimer's disease (AD), implicating amyloid-β (Aβ) production, neurofibrillary tangle formation, and neuronal apoptosis. The activation of 5′ AMP-activated protein kinase (AMPK) has been linked to aberrant processing of amyloid-β protein precursor (AβPP), and AMPK signaling controls Aβ metabolism. It is possible that GSK-3β regulated the activation of the AMPK pathway. To test this hypothesis, the influence of GSK-3β on the expression of AβPP cleavage enzyme (BACE), Aβ, and AMPK in the SH-SY5Y and AβPP695 cells line through three inhibitors of GSK-3β was analyzed. Expression of Aβ, AMPK, and pAMPK172 was measured by Western blot, and BACE was tested by Western blot and RT-PCR. This study demonstrated that suppression of GSK-3β activity, through specific inhibitors, dramatically down-regulated Aβ generation in human SH-SY5Y and SH-SY5Y-AβPP695 cells by enhancing AMPK activity to down-regulate Aβ. These results suggest GSK-3β inhibitors may be promising agents in the prevention and treatment of AD.
