Microglia activation toward M1 pro-inflammatory phenotype represents one of the earliest events of neurological disorders. Therefore, reducing microglia activation should inhibit neuroinflammation, thereby delaying the progression of neurodegeneration. Recently, we pointed out the role of STAT1 signaling in hypoxia-induced M1 activation and proposed STAT1 as a suitable molecular target for the prevention and treatment of neurodegeneration. Myricetin (MYR) is a natural flavonoid that exhibits a specific anti-STAT1 activity correlated with its direct interaction with STAT1 protein itself. Herein, we investigated the anti-inflammatory effect of MYR and its ability to protect neurons from death in an in vitro model of neurotoxicity using the neuroblast-like SH-SY5Y cells that were exposed to conditioned media from hypoxia-activated microglia BV2 cells. We demonstrate that MYR pretreatment is able to switch off hypoxia-induced M1 microglia polarization through the inhibition of STAT1 signaling. The analysis of the molecular mechanism suggests that the direct interaction of MYR with STAT1 impairs its S-glutathionylation and phosphorylation. Moreover, treatment of SH-SY5Y cells with conditioned medium from hypoxia-activated microglia pretreated with MYR produced a significant reduction in neuronal viability. Our data indicate that MYR may represent a promising candidate for prevention and treatment of neuroinflammation in neurodegenerative disorders.

The anti-STAT1 polyphenol myricetin inhibits M1 microglia activation and counteracts neuronal death / Boriero, D.; Carcereri de Prati, A.; Antonini, L.; Ragno, R.; Sohji, K.; Mariotto, S.; Butturini, E.. - In: THE FEBS JOURNAL. - ISSN 1742-464X. - (2020). [10.1111/febs.15577]

The anti-STAT1 polyphenol myricetin inhibits M1 microglia activation and counteracts neuronal death

Antonini L.;Ragno R.;
2020

Abstract

Microglia activation toward M1 pro-inflammatory phenotype represents one of the earliest events of neurological disorders. Therefore, reducing microglia activation should inhibit neuroinflammation, thereby delaying the progression of neurodegeneration. Recently, we pointed out the role of STAT1 signaling in hypoxia-induced M1 activation and proposed STAT1 as a suitable molecular target for the prevention and treatment of neurodegeneration. Myricetin (MYR) is a natural flavonoid that exhibits a specific anti-STAT1 activity correlated with its direct interaction with STAT1 protein itself. Herein, we investigated the anti-inflammatory effect of MYR and its ability to protect neurons from death in an in vitro model of neurotoxicity using the neuroblast-like SH-SY5Y cells that were exposed to conditioned media from hypoxia-activated microglia BV2 cells. We demonstrate that MYR pretreatment is able to switch off hypoxia-induced M1 microglia polarization through the inhibition of STAT1 signaling. The analysis of the molecular mechanism suggests that the direct interaction of MYR with STAT1 impairs its S-glutathionylation and phosphorylation. Moreover, treatment of SH-SY5Y cells with conditioned medium from hypoxia-activated microglia pretreated with MYR produced a significant reduction in neuronal viability. Our data indicate that MYR may represent a promising candidate for prevention and treatment of neuroinflammation in neurodegenerative disorders.
2020
microglia activation; natural compound; neuroinflammation; neuronal death; STAT1
01 Pubblicazione su rivista::01a Articolo in rivista
The anti-STAT1 polyphenol myricetin inhibits M1 microglia activation and counteracts neuronal death / Boriero, D.; Carcereri de Prati, A.; Antonini, L.; Ragno, R.; Sohji, K.; Mariotto, S.; Butturini, E.. - In: THE FEBS JOURNAL. - ISSN 1742-464X. - (2020). [10.1111/febs.15577]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1511704
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