A Novel Resveratrol-Induced Pathway Increases Neuron-Derived Cell Resilience against Oxidative Stress

A promising therapeutic strategy to delay and/or prevent the onset of neurodegenerative diseases (NDs) could be to restore neuroprotective pathways physiologically triggered by neurons against stress injury. Recently, we identified the accumulation of neuroglobin (NGB) in neuronal cells, induced by the 17 beta-estradiol (E2)/estrogen receptor beta (ER beta) axis, as a protective response that increases mitochondria functionality and prevents the activation of apoptosis, increasing neuron resilience against oxidative stress. Here, we would verify if resveratrol (Res), an ER beta ligand, could reactivate NGB accumulation and its protective effects against oxidative stress in neuronal-derived cells (i.e., SH-SY5Y cells). Our results demonstrate that ER beta/NGB is a novel pathway triggered by low Res concentrations that lead to rapid and persistent NGB accumulation in the cytosol and in mitochondria, where the protein contributes to reducing the apoptotic death induced by hydrogen peroxide (H2O2). Intriguingly, Res conjugation with gold nanoparticles increases the stilbene efficacy in enhancing neuron resilience against oxidative stress. As a whole, ER beta/NGB axis regulation is a novel mechanism triggered by low concentration of Res to regulate, specifically, the neuronal cell resilience against oxidative stress reducing the triggering of the apoptotic cascade.

Automated summary

A promising therapeutic strategy to delay and/or prevent neurodegenerative diseases could be the restoration of neuroprotective pathways activated by neurons to defend against stress injury. The accumulation of neuroglobin (NGB), induced by the E2/ER beta axis, has been identified as a protective response that enhances mitochondria functionality and prevents apoptosis activation, increasing neuron resilience against oxidative stress. Resveratrol (Res), an ER beta ligand, has shown the ability to reactivate NGB accumulation and exert protective effects against oxidative stress in neuronal-derived cells.