title: Curcumin-mediated neuroprotection against amyloid-β-induced mitochondrial dysfunction involves the inhibition of GSK-3β.
abstract: The deposition of amyloid-β (Aβ) peptides in senile plaques is one of pathological hallmarks of Alzheimer's disease (AD). Mitochondrial dysfunction is an early event of cell apoptosis. Increasing evidence indicates that Aβ induces neuronal apoptosis through mitochondrial dysfunction. Curcumin, an anti-oxidative component of turmeric (Curcuma longa), has shown anti-tumor, anti-inflammatory, and anti-oxidative properties. In this study, we investigated the protective effects of curcumin against mitochondrial dysfunction induced by Aβ. Based on the assay results of mitochondrial metabolic markers, we found that curcumin protects human neuroblastoma SH-SY5Y cells against the Aβ-induced damage of mitochondrial energy metabolism. Curcumin inhibits Aβ-induced mitochondrial depolarization of membrane potential (Δψm) and suppresses mitochondrial apoptosis-related proteins including cytochrome c, caspase-3, and Bax, which are activated by Aβ. Aβ-induced disturbances of redox state are linked to mitochondrial dysfunction. Curcumin normalizes cellular antioxidant enzymes (including SOD and catalase) in both protein expression and activity and decreases oxidative stress level in Aβ-treated cells. Both total GSK-3β expression and phospho-Ser9 GSK-3β (pSer9-GSK-3β) are down-regulated in the cells pre-treated with curcumin. This study demonstrates curcumin-mediated neuroprotection against Aβ-induced mitochondrial metabolic deficiency and abnormal alteration of oxidative stress. Inhibition of GSK-3β is involved in the protection of curcumin against Aβ-induced mitochondrial dysfunction.
authors.affiliation: College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China. hanchang@ygi.edu.cn
authors.forename: Han-Chang
authors.initials: HC
authors.lastname: Huang
authors.forename: Ke
authors.initials: K
authors.lastname: Xu
authors.forename: Zhao-Feng
authors.initials: ZF
authors.lastname: Jiang
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D045744:Cell Line, Tumor; D003474:Curcumin / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000633:toxicity*
chemical_list: D016229:Amyloid beta-Peptides; D004791:Enzyme Inhibitors; D018696:Neuroprotective Agents; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; D003474:Curcumin