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
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.