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The Neuroprotective Effect of GM-1 Ganglioside on the Amyloid-Beta-Induced Oxidative Stress in PC-12 Cells Mediated by Nrf-2/ARE Signaling Pathway

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Abstract

Alzheimer’s disease (AD) is characterized by the accumulation of amyloid-β (Aβ) plaques, tau tangles, neuroinflammation, oxidative stress, and progressive memory deficits. Aβ deposition could exacerbate oxidative damage and cellular apoptosis. GM-1 ganglioside (GM-1) has previously been reported to exhibit neuroprotective effects in rodents and patients with AD. However, the substantial impacts and mechanism of GM-1 on Aβ-induced oxidative stress remain elusive. The present study used PC-12 pheochromocytoma cells treated with Aβ25–35 peptide to construct the AD model in vitro. Aβ25–35 administration alone inhibited cell viability and facilitated cell apoptosis in the range doses of 10 μM to 30 μM. At the same time, GM-1 supplementation promoted cell proliferation and rescued cell apoptosis in a dose-dependent fashion ranging from 5 to 30 μM. In parallel, GM-1 treatment alleviated Aβ-induced oxidative stress by increasing the level of antioxidant enzymes and decreasing the content of malondialdehyde (MDA). The nuclear factor-E2-related factor 2 (Nrf2) is a crucial mediator of antioxidant response. We reported herein that GM-1 could activate Nrf-2 in the PC-12 cells co-treated with Aβ25–35, following with the activated expression of antioxidant response elements (ARE)-mediated antioxidant and detoxifying genes. Consistently, knock-down of Nrf-2 via siRNA abolished the beneficial decrease of Aβ-induced oxidative stress by GM-1 treatment, indicating that GM-1-improved oxidative stress was regulated by the Nrf-2 signaling pathway. Collectively, GM-1 could alleviate Aβ25–35-induced oxidative damage mediated through the Nrf-2/ARE signaling pathway, which might be a potential agent for AD treatment.

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Acknowledgements

This work was supported by the Hangzhou Municipal Health Science and Technology Plan (Project No. 2016A12) and the Construction Fund of Key Medical Disciplines of Hangzhou (Grant No. OO20200055).

Funding

Hangzhou Municipal Health Science and Technology Plan (Project No. 2016A12); The Construction Fund of Key Medical Disciplines of Hangzhou (Grant No. OO20200055).

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Authors and Affiliations

  1. Department of Geriatric Medicine, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, No. 261, Huansha Road, Shangcheng District, Hangzhou, 310006, China

    Xiaonan Wang, Bei Li, Xiaohong Yu, Ye Zhou & Yue Gao

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XW, BL, XY, YZ, YG, collected samples, acquired and analyzed data. XW wrote the manuscript. XW and YG contributed to the study concept, designed and revised the manuscript.

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Correspondence to Yue Gao.

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Wang, X., Li, B., Yu, X. et al. The Neuroprotective Effect of GM-1 Ganglioside on the Amyloid-Beta-Induced Oxidative Stress in PC-12 Cells Mediated by Nrf-2/ARE Signaling Pathway. Neurochem Res 47, 2405–2415 (2022). https://doi.org/10.1007/s11064-022-03635-8

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