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.

Schisandrin B Enhances Glutathione Redox Cycling and Protects Against β-amyloid-induced Apoptosis in Human Neuroblastoma SH-SY5Y Cells: A Comparative Study of Various Phytochemicals

“…Among the four tested phytochemicals, only ()Sch B and EGCG were found to protect against A-induced apoptosis in SH-SY5Y cells. However, other reports have demonstrated that Cur and Rev can protect against -induced toxicity in primary neurons and neuroblastoma cells [28,29]. The discrepancy between the present study and earlier studies by other laboratories may be related to differences in drug treatment protocols.…”

“…The discrepancy between the present study and earlier studies by other laboratories may be related to differences in drug treatment protocols. In previous studies, exposure to Cur or Rev was immediately followed by challenge [28,29], whereas in the present study, phytochemical-pre-incubated cells were further incubated with fresh medium without phytochemicals for 16 h before being subjected to  challenge. The glutathione antioxidant response, if it occurs, is elicited during the post-drug exposure incubation period.…”

Attenuation of Oxidative Stress-Induced Osteoblast Apoptosis by Curcumin is Associated with Preservation of Mitochondrial Functions and Increased Akt-GSK3β Signaling

“…Some studies indicate that curcumin treatment attenuates pathological conditions through activation of prosurvival signaling pathways [26,27]. To a large extent, these protective effects of curcumin have been attributed to its strong activity against mitochondrial dysfunction [28,29]. Because of its potent antioxidant properties and an anti-apoptotic activity in noncancerous cells, we hypothesized that curcumin might effectively protect osteoblasts from oxidative damage.…”

Mori Fructus improves cognitive and neuronal dysfunction induced by beta-amyloid toxicity through the GSK-3β pathway in vitro and in vivo

“…However, co-treatment with ME and LY294002 failed to result in a significant inhibition of phosphorylation. In addition, GSK-3β promotes ROS generation and intrinsic apoptotic signaling, which is often induced by intracellular damage that leads to mitochondrial release of cytochrome c and the activation of intracellular cysteine proteases known as caspases, eventually resulting in apoptosis (Huang et al, 2012;Mines et al, 2011). In this study, ME treatment reduced oxidative stress, which generally contributes to apoptosis (Zhang et al, 2005).…”