Modulation of Nrf2/ARE Pathway by Food Polyphenols: A Nutritional Neuroprotective Strategy for Cognitive and Neurodegenerative Disorders |
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Authors: | Giovanni Scapagnini Vasto Sonya Abraham G Nader Caruso Calogero Davide Zella Galvano Fabio |
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Institution: | (1) Department of Health Sciences, University of Molise, Campobasso, Italy;(2) Immunosenescence Unit, Department of Pathobiology and Biomedical Methodologies, University of Palermo, Palermo, Italy;(3) Department of Physiology and Pharmacology, College of Medicine, University of Toledo, Toledo, OH, USA;(4) Department of Biological Chemistry, Medical Chemistry and Molecular Biology, University of Catania, Catania, Italy;(5) Department of Biochemistry and Molecular Biology, Institute of Human Virology-School of Medicine, University of Maryland, Baltimore, MD, USA |
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Abstract: | In recent years, there has been a growing interest, supported by a large number of experimental and epidemiological studies,
for the beneficial effects of some phenolic substances, contained in commonly used spices and herbs, in preventing various
age-related pathologic conditions, ranging from cancer to neurodegenerative diseases. Although the exact mechanisms by which
polyphenols promote these effects remain to be elucidated, several reports have shown their ability to stimulate a general
xenobiotic response in the target cells, activating multiple defense genes. Data from our and other laboratories have previously
demonstrated that curcumin, the yellow pigment of curry, strongly induces heme-oxygenase-1 (HO-1) expression and activity
in different brain cells via the activation of heterodimers of NF-E2-related factors 2 (Nrf2)/antioxidant responsive element (ARE) pathway. Many studies clearly demonstrate that activation ofNrf2 target genes,
and particularly HO-1, in astrocytes and neurons is strongly protective against inflammation, oxidative damage, and cell death.
In the central nervous system, the HO system has been reported to be very active, and its modulation seems to play a crucial
role in the pathogenesis of neurodegenerative disorders. Recent and unpublished data from our group revealed that low concentrations
of epigallocatechin-3-gallate, the major green tea catechin, induces HO-1 by ARE/Nrf2 pathway in hippocampal neurons, and
by this induction, it is able to protect neurons against different models of oxidative damages. Furthermore, we have demonstrated
that other phenolics, such as caffeic acid phenethyl ester and ethyl ferulate, are also able to protect neurons via HO-1 induction.
These studies identify a novel class of compounds that could be used for therapeutic purposes as preventive agents against
cognitive decline. |
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