Down-regulation of amyloid-β through AMPK activation by inhibitors of GSK-3β in SH-SY5Y and SH-SY5Y-AβPP695 cells.
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.
Department of Neurology, The Affiliated Hospital of Guangdong Medical College, Zhanjiang, China.
Zhiyou
Z
Cai
Benyi
B
Li
Keshen
K
Li
Bin
B
Zhao
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D004789:Enzyme Activation; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000494:pharmacology
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D047428:Protein Kinase Inhibitors; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; D055372:AMP-Activated Protein Kinases