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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2023

Open Access 01-12-2023 | Parkinson's Disease | Research

Neuroprotective effects of GSK-343 in an in vivo model of MPTP-induced nigrostriatal degeneration

Authors: Deborah Mannino, Sarah Adriana Scuderi, Giovanna Casili, Valentina Bova, Laura Cucinotta, Marika Lanza, Alessia Filippone, Emanuela Esposito, Irene Paterniti

Published in: Journal of Neuroinflammation | Issue 1/2023

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Abstract

Parkinson’s disease (PD) is characterized by the degeneration of dopaminergic nigrostriatal neurons, which causes disabling motor disorders. Scientific findings support the role of epigenetics mechanism in the development and progression of many neurodegenerative diseases, including PD. In this field, some studies highlighted an upregulation of Enhancer of zeste homolog 2 (EZH2) in the brains of PD patients, indicating the possible pathogenic role of this methyltransferase in PD. The aim of this study was to evaluate the neuroprotective effects of GSK-343, an EZH2 inhibitor, in an in vivo model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic degeneration. Specifically, nigrostriatal degeneration was induced by MPTP intraperitoneal injection. GSK-343 was administered intraperitoneally daily at doses of 1 mg/kg, 5 mg/kg and 10 mg/kg, mice were killed 7 days after MPTP injection. Our results demonstrated that GSK-343 treatment significantly improved behavioral deficits and reduced the alteration of PD hallmarks. Furthermore, GSK-343 administration significantly attenuated the neuroinflammatory state through the modulation of canonical and non-canonical NF-κB/IκBα pathway as well as the cytokines expression and glia activation, also reducing the apoptosis process. In conclusion, the obtained results provide further evidence that epigenetic mechanisms play a pathogenic role in PD demonstrating that the inhibition of EZH2, mediated by GSK-343, could be considered a valuable pharmacological strategy for PD.
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Metadata
Title
Neuroprotective effects of GSK-343 in an in vivo model of MPTP-induced nigrostriatal degeneration
Authors
Deborah Mannino
Sarah Adriana Scuderi
Giovanna Casili
Valentina Bova
Laura Cucinotta
Marika Lanza
Alessia Filippone
Emanuela Esposito
Irene Paterniti
Publication date
01-12-2023
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2023
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-023-02842-6

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