Alzheimer's disease (AD) is characterized by amyloid-beta peptide deposition, increased activated microglia, and progressive loss of neurons in the brain. Although A beta(1-40) can elicit inflammation in microglia, the intracellular signaling events mediating these effects are poorly defined. Here we show that cell-free supernatant from A beta(1-40)-treated THP-1 monocytes induced cytotoxicity towards neuroblastoma SK-N-SH cells. Exposure of THP-1 monocytes to A beta(1-40) leads to increased tyrosine phosphorylation and extracellular signaling-regulated kinase (ERK) and increased levels of inflammatory cytokines (IL-1 beta, IL-8, and TNF-alpha) in the supernatant of THP-1 monocytes. Pretreatment of THP-1 monocytes with either a protein tyrosine kinase (PTK) inhibitor or an ERK inhibitor protects SK-N-SH cells from the cytotoxic effect of conditional supernatant from A beta(1-40)-treated THP-1 monocytes. A beta(1-40)-treated THP-1 monocytes also lead to upregulation of cyclooxygenase-2 and iNOS expression and increased of nitric oxide production. These results suggest that A beta(1-40)-induced activation of PTK/MEK/ERK pathway in THP-1 monocytes leads to the release of inflammatory factors that are toxic to SK-N-SH cells and might contribute to the onset of AD. Crown Copyright (C) 2011 Published by Elsevier B.V. All rights reserved.
基金：
National Key Basic Research 973 Program of China (No. 2003CB517104), the National Natural Science Foundation of China (No. 90709011, 30472184, 30973513, 30701092, 81001656),
and Beijing Science and Technology Program (No. D0206001043191).
第一作者机构：[a]Department of Pharmacology, Xuan-wu Hospital of Capital Medical University, Education Ministry Key Laboratory for Neurodegenerative Disease, 45 Chang-chun Street, Beijing, 100053, PR China
共同第一作者：
通讯作者：
通讯机构：[a]Department of Pharmacology, Xuan-wu Hospital of Capital Medical University, Education Ministry Key Laboratory for Neurodegenerative Disease, 45 Chang-chun Street, Beijing, 100053, PR China
推荐引用方式(GB/T 7714)：
Lin-Lin Yin,Wei Li,Yan-Qi Chu,et al.ERK pathway activation is required for amyloid-beta(1-40)-induced neurotoxicity of THP-1 human monocytes towards SK-N-SH neuroblastoma[J].BRAIN RESEARCH.2011,1378:45186.doi:10.1016/j.brainres.2011.01.013.
APA：
Lin-Lin Yin,Wei Li,Yan-Qi Chu&Lin Li.(2011).ERK pathway activation is required for amyloid-beta(1-40)-induced neurotoxicity of THP-1 human monocytes towards SK-N-SH neuroblastoma.BRAIN RESEARCH,1378,
MLA：
Lin-Lin Yin,et al."ERK pathway activation is required for amyloid-beta(1-40)-induced neurotoxicity of THP-1 human monocytes towards SK-N-SH neuroblastoma".BRAIN RESEARCH 1378.(2011):45186
