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

• DOI: 10.2174/1567205015666181022093359
• Publication Date: 2018-10-22T12:02:11Z
• Authors: Zhenkui Ren; Mei Yang; Zhizhong Guan; Wenfeng Yu
• Keywords: Cerebral Cortex; Male; 0301 basic medicine; Nicotine; Amyloid beta-Peptides; Morpholines; Primary Cell Culture; Mice, Transgenic; Crystallins; Protein Aggregation, Pathological; Mice, Inbred C57BL; Phosphatidylinositol 3-Kinases; 03 medical and health sciences; Neuroprotective Agents; Chromones; Astrocytes; Animals; Humans; Nicotinic Agonists; Proto-Oncogene Proteins c-akt; Cells, Cultured; Phosphoinositide-3 Kinase Inhibitors

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 AD brains is closely associated with deposits. However, relationships between astrocytic nAChRs remain unclear.The oligomers levels cell lysates culture medium were measured after treatment nicotine or co-treatment a Phosphatidylinositol 3-Kinase (PI3K)-protein kinase B (Akt) inhibitor. The level αB-Crystallin (Cryab) treated for different times co-treated nAChR antagonists as well co-incubated PI3K mitogen-activated protein 1/2 (MEK1/2) inhibitor was determined by western blotting.In this study, pre-treatment primary markedly inhibited upregulated endogenous Cryab, while nicotine-mediated neuroprotective effect reversed selective antagonist. Furthermore, neuroprotection against suppressed LY294002, Pre-treatment increased phosphorylated Akt, effector astrocytes.α7 activation PI3K/Akt signaling transduction contributed to nicotinemediated modulating Cryab.