Reversal of Beta-Amyloid-Induced Neurotoxicity in PC12 Cells by Curcumin, the Important Role of ROS-Mediated Signaling and ERK Pathway

Abstract

Progressive accumulation of beta-amyloid (Aβ) will form the senile plaques and cause oxidative damage and neuronal cell death, which was accepted as the major pathological mechanism to the Alzheimer's disease (AD). Hence, inhibition of Aβ-induced oxidative damage and neuronal cell apoptosis by agents with potential antioxidant properties represents one of the most effective strategies in combating human AD. Curcumin (Cur) a natural extraction from curcuma longa has potential of pharmacological efficacy, including the benefit to antagonize Aβ-induced neurotoxicity. However, the molecular mechanism remains elusive. The present study evaluated the protective effect of Cur against Aβ-induced cytotoxicity and apoptosis in PC12 cells and investigated the underlying mechanism. The results showed that Cur markedly reduced Aβ-induced cytotoxicity by inhibition of mitochondria-mediated apoptosis through regulation of Bcl-2 family. The PARP cleavage, caspases activation, and ROS-mediated DNA damage induced by Aβ were all significantly blocked by Cur. Moreover, regulation of p38 MAPK and AKT pathways both contributed to this protective potency. Our findings suggested that Cur could effectively suppress Aβ-induced cytotoxicity and apoptosis by inhibition of ROS-mediated oxidative damage and regulation of ERK pathway, which validated its therapeutic potential in chemoprevention and chemotherapy of Aβ-induced neurotoxicity.

Astaxanthin Attenuates Homocysteine-Induced Cardiotoxicity in Vitro and in Vivo by Inhibiting Mitochondrial Dysfunction and Oxidative Damage

“…Mitochondria integrates the intrinsic and extrinsic signals and plays important role in lunching mitochondria-mediated apoptosis (Zhu et al, 2016 ). Mitochondrial membrane permeabilization acts as an important event in inducing cell apoptotic death in response to apoptotic stimuli (Kroemer et al, 2007 ; Zhu et al, 2016 ; Fan et al, 2017b ). Bcl-2 family, including the pro-apoptotic and anti-apoptotic members, has been confirmed as essential factors in regulating mitochondria-mediated apoptosis pathway (Cory and Adams, 2002 ).…”

Neuroprotective Effects of Limonene (+) against Aβ42-Induced Neurotoxicity in a <i>Drosophila</i> Model of Alzheimer’s Disease

“…4B, C), which implies that limonene (+) does not act directly as an ERK inhibitor. Given that markedly increased oxidative stress in the brains of individuals with AD causes phosphorylation of ERK [33][34][35][36] and that limonene (+) has antioxidant activity, 30) it is expected that limonene (+) would reduce ERK phosphorylation in the brains of Aβ42-expressing flies by ROS scavenging. To test this hypothesis, we performed experiments to examine whether limonene (+) could inhibit ERK phosphorylation induced by H 2 O 2 in the fly brain.…”

Integrated communications between cyclooxygenase‐2 and Alzheimer's disease

“…Compelling evidence has demonstrated that Ab produces toxicity in neurons (73,74) and in glial cells (75,76). These observations have been corroborated in mice and rats (77,78), especially Tg2576 mice, which are a canonical AD experimental model.…”