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.

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 10μM to 30μM. At the same time, GM-1 supplementation promoted cell proliferation and rescued cell apoptosis in a dose-dependent fashion ranging from 5 to 30μM. 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.