BDMC protects AD in vitro via AMPK and SIRT1

Chenlin Xu; Zijian Xiao; Heng Wu; Guijuan Zhou; Duanqun He; Yunqian Chang; Yihui Li; Gang Wang; Ming Xie

doi:10.1515/tnsci-2020-0140

BDMC protects AD in vitro via AMPK and SIRT1

Transl Neurosci. 2020 Sep 9;11(1):319-327. doi: 10.1515/tnsci-2020-0140. eCollection 2020.

Authors

Chenlin Xu^{1

2}, Zijian Xiao¹, Heng Wu¹, Guijuan Zhou¹, Duanqun He¹, Yunqian Chang¹, Yihui Li¹, Gang Wang³, Ming Xie¹

Affiliations

¹ The First Affiliated Hospital, University of South China, Hengyang, Hunan 421001, People's Republic of China.
² Xiangxi Autonomous Prefecture People's Hospital, Jishou, Hunan 416000, People's Republic of China.
³ Department of Rehabilitation, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, People's Republic of China.

Abstract

Background: Alzheimer's disease (AD) is a common neurodegenerative disorder without any satisfactory therapeutic approaches. AD is mainly characterized by the deposition of β-amyloid protein (Aβ) and extensive neuronal cell death. Curcumin, with anti-oxidative stress (OS) and cell apoptosis properties, plays essential roles in AD. However, whether bisdemethoxycurcumin (BDMC), a derivative of curcumin, can exert a neuroprotective effect in AD remains to be elucidated.

Methods: In this study, SK-N-SH cells were used to establish an in vitro model to investigate the effects of BDMC on the Aβ_1-42-induced neurotoxicity. SK-N-SH cells were pretreated with BDMC and with or without compound C and EX527 for 30 min after co-incubation with rotenone for 24 h. Subsequently, western blotting, cell viability assay and SOD and GSH activity measurement were performed.

Results: BDMC increased the cell survival, anti-OS ability, AMPK phosphorylation levels and SIRT1 in SK-N-SH cells treated with Aβ_1-42. However, after treatment with compound C, an AMPK inhibitor, and EX527, an SIRT1inhibitor, the neuroprotective roles of BDMC on SK-N-SH cells treated with Aβ_1-42 were inhibited.

Conclusion: These results suggest that BDMC exerts a neuroprotective role on SK-N-SH cells in vitro via AMPK/SIRT1 signaling, laying the foundation for the application of BDMC in the treatment of neurodegenerative diseases related to AMPK/SIRT1 signaling.

Keywords: AMPK; Alzheimer’s disease (AD); SIRT1; bisdemethoxycurcumin (BDMC).