Astrocytic α7 Nicotinic Receptor Activation Inhibits Amyloid-β Aggregation by Upregulating Endogenous αB-crystallin through the PI3K/Akt Signaling Pathway

Author(s): Zhenkui Ren, Mei Yang, Zhizhong Guan, Wenfeng Yu*

Journal Name: Current Alzheimer Research

Volume 16 , Issue 1 , 2019

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Background: β-amyloid (Aβ) aggregation plays an important role in the pathogenesis of Alzheimer’s disease (AD), and astrocytes can significantly inhibit Aβ aggregation. Astrocytic α7 Neuronal Nicotinic Acetylcholine Receptor (nAChR) upregulation detected in the AD brains is closely associated with Aβ deposits. However, the relationships between the astrocytic α7 nAChRs and Aβ aggregation remain unclear.

Methods: The Aβ oligomers levels in astrocytic cell lysates and culture medium were measured after treatment with nicotine or co-treatment with a Phosphatidylinositol 3-Kinase (PI3K)-protein kinase B (Akt) inhibitor. The level of αB-Crystallin (Cryab) in astrocytes treated with nicotine for different times or co-treated with α7 nAChR antagonists as well as co-incubated with a PI3K or mitogen-activated protein kinase kinase 1/2 (MEK1/2) inhibitor was determined by western blotting.

Results: In this study, nicotine pre-treatment in primary astrocytes markedly inhibited Aβ aggregation and upregulated endogenous astrocytic Cryab, while the nicotine-mediated neuroprotective effect was reversed by pre-treatment with a selective α7 nAChR antagonist. Furthermore, this neuroprotection against Aβ aggregation was suppressed by LY294002, a PI3K inhibitor. Pre-treatment with nicotine significantly increased the levels of phosphorylated Akt, an effector of PI3K in astrocytes.

Conclusion: α7 nAChR activation and PI3K/Akt signaling transduction contributed to nicotinemediated neuroprotection against Aβ aggregation by modulating endogenous astrocytic Cryab.

Keywords: Alzheimer's disease, β -amyloid aggregation, α7 neuronal nicotinic acetylcholine receptors, PI3K/Akt signaling pathway, αB-crystallin, dementia.

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Year: 2019
Page: [39 - 48]
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DOI: 10.2174/1567205015666181022093359
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