title: Salubrinal attenuates β-amyloid-induced neuronal death and microglial activation by inhibition of the NF-κB pathway.
abstract: Alzheimer's disease (AD) is characterized by the deposition of β-amyloid (Aβ) peptides in the brain, inducing neuronal cell death and microglial activation. Endoplasmic reticulum (ER) stress has been proposed to be a mediator of Aβ neurotoxicity. In this study, we test whether salubrinal, an ER stress inhibitor, can protect against Aβ-mediated neurotoxicity. We show in rat primary cortical neurons and mouse microglial BV-2 cells that short-term treatment with salubrinal attenuates Aβ-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 IκB kinase (IKK) activation, IκB degradation, and the subsequent nuclear factor-kappa B (NF-κB) activation. These results elucidate inhibition of the NF-κB pathway as a new mechanism responsible for the protective effects of salubrinal against Aβ neurotoxicity. This study also suggests that modulation of Aβ-induced NF-κB activation could be a potential therapeutic strategy for Alzheimer's disease.
authors: Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, College of Medicine, Xiamen University, Xiamen, Fujian, China.
authors: Xiumei
authors: X
authors: Huang
authors: Yaomin
authors: Y
authors: Chen
authors: Han
authors: H
authors: Zhang
authors: Qilin
authors: Q
authors: Ma
authors: Yun-wu
authors: YW
authors: Zhang
authors: Huaxi
authors: H
authors: Xu
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000633:toxicity; D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D002934:Cinnamates / Q000494:pharmacology*; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000502:physiology; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology; D061251:Primary Cell Culture; D051381:Rats; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D016229:Amyloid beta-Peptides; D002934:Cinnamates; D016328:NF-kappa B; D018696:Neuroprotective Agents; C496827:salubrinal; D013890:Thiourea