Abstract
Dietary antioxidants may be useful in counteracting the chronic inflammatory status in neurodegenerative diseases by reducing oxidative stress due to accumulation of reactive oxygen species (ROS). In this study, we newly described the efficacy of a number of dietary antioxidants (polyphenols, carotenoids, thiolic compounds, and oligoelements) on viability of neuronal PC12 cells following Nerve Growth Factor (NGF) deprivation, a model of age-related decrease of neurotrophic support that triggers neuronal loss. Neuroprotection by antioxidants during NGF deprivation for 24 h was largely dependent on their concentrations: all dietary antioxidants were able to efficiently support cell viability by reducing ROS levels and restoring mitochondrial function, while preserving the neuronal morphology. Moreover, ROS reduction and neuroprotection during NGF withdrawal were also achieved with defined cocktails of 3–6 different antioxidants at concentrations 5–60 times lower than those used in single treatments, suggesting that their antioxidant activity was preserved also at very low concentrations. Overall, these data indicate the beneficial effects of antioxidants against oxidative stress induced by decreased NGF availability and suggest that defined cocktails of dietary factors at low concentrations might be a suitable strategy to reduce oxidative damage in neurodegenerative diseases, while limiting possible side effects.
Highlights
Oxidative stress and mitochondrial dysfunction are common outcomes of inflammatory conditions which have been involved in the pathogenesis of chronic neurodegenerative disorders, including Alzheimer’s disease (AD), Parkinson’s disease (PD), Multiple Sclerosis (MS), and Amyotrophic Lateral Sclerosis (ALS) [1,2,3]
We provide new evidence about the efficacy of a number of dietary antioxidants in restoring cell viability under conditions of Nerve Growth Factor (NGF) deprivation by decreasing oxidative stress and mitochondrial dysfunction
To examine the activity of these molecules, we used NGF-differentiated PC12 cells, which are widely used to investigate molecular events linked to NGF deprivation and Aβ toxicity [10, 44], as well as to study intracellular signaling induced by oxidative stress or neurotoxins involved in PD [4, 14, 45, 46]
Summary
Oxidative stress and mitochondrial dysfunction are common outcomes of inflammatory conditions which have been involved in the pathogenesis of chronic neurodegenerative disorders, including Alzheimer’s disease (AD), Parkinson’s disease (PD), Multiple Sclerosis (MS), and Amyotrophic Lateral Sclerosis (ALS) [1,2,3]. Age-dependent decrease of Nerve Growth Factor (NGF) [5,6,7] has been functionally linked to sporadic forms of AD because of its role in regulating survival and synaptic plasticity of basal forebrain cholinergic neurons [8]. Molecular mechanisms of apoptotic death triggered by decreased NGF availability have been largely elucidated in PC12 cells and primary neurons [5]; they involve oxidative stress and mitochondrial dysfunction [10, 11], due to the role of NGF in regulating the balance of proapoptotic. The increase of free radicals causes oxidative damage to mitochondrial proteins, lipids, and DNA and leads to decreased mitochondrial membrane potential and ATP depletion
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