Salubrinal attenuates β-amyloid-induced neuronal death and microglial activation by inhibition of the NF-κB pathway

NEUROBIOLOGY OF AGING

卷:33

Article

Huang, Xiumei²  Chen, Yaomin¹  Zhang, Han^1,2  Ma, Qilin³  Zhang, Yun-wu^1,2  Xu, Huaxi^1,2 

[1] Sanford Burnham Med Res Inst, Neurodegenerat Dis Res Program, La Jolla, CA 92037 USA

[2] Xiamen Univ, Coll Med, Fujian Prov Key Lab Neurodegenerat Dis & Aging Re, Xiamen, Fujian, Peoples R China

[3] Xiamen Univ, Dept Neurol, Affiliated Hosp 1, Xiamen, Fujian, Peoples R China

关键词: Alzheimer's disease;    Salubrinal;    beta-amyloid;    NF-kappa B;   

DOI  :  10.1016/j.neurobiolaging.2011.10.007

来源: Elsevier

【 摘 要 】

Alzheimer's disease (AD) is characterized by the deposition of beta-amyloid (A beta) peptides in the brain, inducing neuronal cell death and microglial activation. Endoplasmic reticulum (ER) stress has been proposed to be a mediator of A beta neurotoxicity. In this study, we test whether salubrinal, an ER stress inhibitor, can protect against A beta-mediated neurotoxicity. We show in rat primary cortical neurons and mouse microglial BV-2 cells that short-term treatment with salubrinal attenuates A beta-induced neuronal death and microglial activation. Remarkably, our results show that salubrinal's neuroprotective effects are not due to inhibition of ER stress. Rather, we demonstrate that salubrinal exerts its effects through the inhibition of I kappa B kinase (IKK) activation, I kappa B degradation, and the subsequent nuclear factor-kappa B (NF-kappa B) activation. These results elucidate inhibition of the NF-kappa B pathway as a new mechanism responsible for the protective effects of salubrinal against A beta neurotoxicity. This study also suggests that modulation of A beta-induced NF-kappa B activation could be a potential therapeutic strategy for Alzheimer's disease. (C) 2012 Elsevier Inc. All rights reserved.

【 授权许可】

Free