TY - JOUR
A2 - Malaguti, Marco
AU - Martorana, Francesca
AU - Foti, Maria
AU - Virtuoso, Assunta
AU - Gaglio, Daniela
AU - Aprea, Federica
AU - Latronico, Tiziana
AU - Rossano, Rocco
AU - Riccio, Paolo
AU - Papa, Michele
AU - Alberghina, Lilia
AU - Colangelo, Anna Maria
PY - 2019
DA - 2019/08/14
TI - Differential Modulation of NF-κB in Neurons and Astrocytes Underlies Neuroprotection and Antigliosis Activity of Natural Antioxidant Molecules
SP - 8056904
VL - 2019
AB - Neuroinflammation, a hallmark of chronic neurodegenerative disorders, is characterized by sustained glial activation and the generation of an inflammatory loop, through the release of cytokines and other neurotoxic mediators that cause oxidative stress and limit functional repair of brain parenchyma. Dietary antioxidants may protect against neurodegenerative diseases by counteracting chronic neuroinflammation and reducing oxidative stress. Here, we describe the effects of a number of natural antioxidants (polyphenols, carotenoids, and thiolic molecules) in rescuing astrocytic function and neuronal viability following glial activation by reducing astrocyte proliferation and restoring astrocytic and neuronal survival and basal levels of reactive oxygen species (ROS). All antioxidant molecules are also effective under conditions of oxidative stress and glutamate toxicity, two maladaptive components of neuroinflammatory processes. Moreover, it is remarkable that their antioxidant and anti-inflammatory activity occurs through differential modulation of NF-κB binding activity in neurons and astrocytes. In fact, we show that inflammatory stimuli promote a significant induction of NF-κB binding activity in astrocytes and its concomitant reduction in neurons. These changes are prevented in astrocytes and neurons pretreated with the antioxidant molecules, suggesting that NF-κB plays a key role in the modulation of survival and anti-inflammatory responses. Finally, we newly demonstrate that effective antigliosis and neuroprotective activity is achieved with a defined cocktail of four natural antioxidants at very low concentrations, suggesting a promising strategy to reduce inflammatory and oxidative damage in neurodegenerative diseases with limited side effects.
SN - 1942-0900
UR - https://doi.org/10.1155/2019/8056904
DO - 10.1155/2019/8056904
JF - Oxidative Medicine and Cellular Longevity
PB - Hindawi
KW -
ER -