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

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

Journal Name: Current Alzheimer Research

Volume 13 , Issue 11 , 2016

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Abstract:

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.

Keywords: Alzheimer's disease, brain, β-amyloid peptide, NF-κBp65, MCP-1, MCP-1α, α3 nAChR.

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Article Details

VOLUME: 13
ISSUE: 11
Year: 2016
Page: [1290 - 1301]
Pages: 12
DOI: 10.2174/1567205013666160703174254
Price: $58

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