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PNU282987 inhibits amyloid‑β aggregation by upregulating astrocytic endogenous αB‑crystallin and HSP‑70 via regulation of the α7AChR, PI3K/Akt/HSF‑1 signaling axis

  • Authors:
    • Zhenkui Ren
    • Zhihui Dong
    • Peng Xie
    • Ju Lv
    • Yumei Hu
    • Zhizhong Guan
    • Chunlin Zhang
    • Wenfeng Yu
  • View Affiliations / Copyright

    Affiliations: Key Laboratory of Endemic and Ethnic Diseases, Ministry of Education, College of Basic Medical Sciences, Guiyang, Guizhou 550004, P.R. China, College of Basic Medical Sciences, Guizhou Medical University, Guiyang, Guizhou 550025, P.R. China
    Copyright: © Ren et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 201-208
    |
    Published online on: May 5, 2020
       https://doi.org/10.3892/mmr.2020.11132
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Abstract

Alzheimer's disease (AD) is a chronic and irreversible neurodegenerative disorder. Abnormal aggregation of the neurotoxic amyloid‑β (Aβ) peptide is an early event in AD. The activation of astrocytic α7 nicotinic acetylcholine receptor (α7 nAChR) can inhibit Aβ aggregation; thus, the molecular mechanism between α7 nAChR activation and Aβ aggregation warrants further investigation. In the present study, Aβ oligomer levels were assessed in astrocytic cell lysates after treatment with PNU282987 (a potent agonist of α7 nAChRs) or co‑treatment with LY294002, a p‑Akt inhibitor. The levels of heat shock factor‑1 (HSF‑1), heat shock protein 70 (HSP‑70), and αB‑crystallin (Cryab) in astrocytes treated with PNU282987 at various time‑points or co‑treated with methyllycaconitine (MLA), a selective α7 nAChR antagonist, as well as co‑incubated with LY294002 were determined by western blotting. HSP‑70 and Cryab levels were determined after HSF‑1 knockdown (KD) in astrocytes. PNU282987 markedly inhibited Aβ aggregation and upregulated HSF‑1, Cryab, and HSP‑70 in primary astrocytes, while the PNU282987‑mediated neuroprotective effect was reversed by pre‑treatment with MLA or LY294002. Moreover, the HSF‑1 KD in astrocytes effectively decreased Cryab, but not HSP‑70 expression. HSF‑1 is necessary for the upregulation of Cryab expression, but not for that of HSP‑70. HSF‑1 and HSP‑70 have a neuroprotective effect. Furthermore, the neuroprotective effect of PNU282987 against Aβ aggregation was mediated by the canonical PI3K/Akt signaling pathway activation.
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Copy and paste a formatted citation
Spandidos Publications style
Ren Z, Dong Z, Xie P, Lv J, Hu Y, Guan Z, Zhang C and Yu W: PNU282987 inhibits amyloid‑β aggregation by upregulating astrocytic endogenous αB‑crystallin and HSP‑70 via regulation of the α7AChR, PI3K/Akt/HSF‑1 signaling axis. Mol Med Rep 22: 201-208, 2020.
APA
Ren, Z., Dong, Z., Xie, P., Lv, J., Hu, Y., Guan, Z. ... Yu, W. (2020). PNU282987 inhibits amyloid‑β aggregation by upregulating astrocytic endogenous αB‑crystallin and HSP‑70 via regulation of the α7AChR, PI3K/Akt/HSF‑1 signaling axis. Molecular Medicine Reports, 22, 201-208. https://doi.org/10.3892/mmr.2020.11132
MLA
Ren, Z., Dong, Z., Xie, P., Lv, J., Hu, Y., Guan, Z., Zhang, C., Yu, W."PNU282987 inhibits amyloid‑β aggregation by upregulating astrocytic endogenous αB‑crystallin and HSP‑70 via regulation of the α7AChR, PI3K/Akt/HSF‑1 signaling axis". Molecular Medicine Reports 22.1 (2020): 201-208.
Chicago
Ren, Z., Dong, Z., Xie, P., Lv, J., Hu, Y., Guan, Z., Zhang, C., Yu, W."PNU282987 inhibits amyloid‑β aggregation by upregulating astrocytic endogenous αB‑crystallin and HSP‑70 via regulation of the α7AChR, PI3K/Akt/HSF‑1 signaling axis". Molecular Medicine Reports 22, no. 1 (2020): 201-208. https://doi.org/10.3892/mmr.2020.11132
Copy and paste a formatted citation
x
Spandidos Publications style
Ren Z, Dong Z, Xie P, Lv J, Hu Y, Guan Z, Zhang C and Yu W: PNU282987 inhibits amyloid‑β aggregation by upregulating astrocytic endogenous αB‑crystallin and HSP‑70 via regulation of the α7AChR, PI3K/Akt/HSF‑1 signaling axis. Mol Med Rep 22: 201-208, 2020.
APA
Ren, Z., Dong, Z., Xie, P., Lv, J., Hu, Y., Guan, Z. ... Yu, W. (2020). PNU282987 inhibits amyloid‑β aggregation by upregulating astrocytic endogenous αB‑crystallin and HSP‑70 via regulation of the α7AChR, PI3K/Akt/HSF‑1 signaling axis. Molecular Medicine Reports, 22, 201-208. https://doi.org/10.3892/mmr.2020.11132
MLA
Ren, Z., Dong, Z., Xie, P., Lv, J., Hu, Y., Guan, Z., Zhang, C., Yu, W."PNU282987 inhibits amyloid‑β aggregation by upregulating astrocytic endogenous αB‑crystallin and HSP‑70 via regulation of the α7AChR, PI3K/Akt/HSF‑1 signaling axis". Molecular Medicine Reports 22.1 (2020): 201-208.
Chicago
Ren, Z., Dong, Z., Xie, P., Lv, J., Hu, Y., Guan, Z., Zhang, C., Yu, W."PNU282987 inhibits amyloid‑β aggregation by upregulating astrocytic endogenous αB‑crystallin and HSP‑70 via regulation of the α7AChR, PI3K/Akt/HSF‑1 signaling axis". Molecular Medicine Reports 22, no. 1 (2020): 201-208. https://doi.org/10.3892/mmr.2020.11132
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