提高阿尔茨海默氏症的大脑NF-κB和炎症趋化因子的水平—个可能涉及α3烟碱乙酰胆碱受体的机制

Title:Elevations in the Levels of NF-κB and Inflammatory Chemotactic Factors in the Brains with Alzheimer’s Disease - One Mechanism May Involve α3 Nicotinic Acetylcholine Receptor

Volume: 13 Issue: 11

Author(s): Yuan Liao, Xiao-Lan Qi, Ying Cao, Wen-Feng Yu, Rivka Ravid, Bengt Winblad, Jin-Jing Pei, Zhi-Zhong Guan

Affiliation:

关键词: 阿尔茨海默氏症、大脑、β-amyloid肽、NF-κBp65、MCP-1、MCP-1α、α3乙酰胆。

摘要: The purpose of this study was to investigate the alterations in the levels of nuclear factor κBp65 (NF-κBp65), monocyte chemoattractant protein 1 (MCP-1/CCL-2) and macrophage inflammatory protein 1α (MIP-1α/CCL-3) in relationship to the expression of α3 nicotinic acetylcholine receptor (nAChR) during the pathogenesis of Alzheimer’s disease (AD). The post-mortem human brains of AD and age-matched control individuals, SH-SY5Y and U87MG cell lines exposed to β-amyloid peptide (Aβ), as well as the SH-SY5Y cells in which α3 nAChR was down-regulated by siRNA were used to study the possible expression changes of the targets such as NF-κBp65, MCP-1, MIP-1α and α3 nAChR. The immunohistochemistry results showed the increased immunoreactivities of NF-κBp65, MCP-1 and MIP-1α in neurons in hippocampal and temporal and frontal regions of AD brains. Levels of NF-κBp65, MCP-1 and MIP-1α at both protein and mRNA levels were all significantly up-regulated in SH-SY5Y and U87MG cells exposed to Aβ1-42, while expression of α3 nAChRs in Aβ1-42 exposed SH-SY5Y cells was attenuated. Interestingly, in the SH-SY5Y cells subjected to α3 nAChR mRNA silencing, expression of NF-κBp65, MCP-1 and MIP-1α was elevated. The elevated expressions of NF- κB and chemokines may be involved by decreased expression of α3 nAChRs during the pathogenesis of AD.

Cite this article as:

Yuan Liao, Xiao-Lan Qi, Ying Cao, Wen-Feng Yu, Rivka Ravid, Bengt Winblad, Jin-Jing Pei, Zhi-Zhong Guan , Elevations in the Levels of NF-κB and Inflammatory Chemotactic Factors in the Brains with Alzheimer’s Disease - One Mechanism May Involve α3 Nicotinic Acetylcholine Receptor, Current Alzheimer Research 2016; 13 (11) . https://dx.doi.org/10.2174/1567205013666160703174254