| Autor: |
Roberto Di Maio, Matthew T. Keeney, Veronika Cechova, Amanda Mortimer, Ahssan Sekandari, Pascal Rowart, J. Timothy Greenamyre, Bruce A. Freeman, Marco Fazzari |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
npj Parkinson's Disease, Vol 9, Iss 1, Pp 1-11 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2373-8057 |
| DOI: |
10.1038/s41531-023-00502-3 |
| Popis: |
Abstract To date there are no therapeutic strategies that limit the progression of Parkinson’s disease (PD). The mechanisms underlying PD-related nigrostriatal neurodegeneration remain incompletely understood, with multiple factors modulating the course of PD pathogenesis. This includes Nrf2-dependent gene expression, oxidative stress, α-synuclein pathology, mitochondrial dysfunction, and neuroinflammation. In vitro and sub-acute in vivo rotenone rat models of PD were used to evaluate the neuroprotective potential of a clinically-safe, multi-target metabolic and inflammatory modulator, the electrophilic fatty acid nitroalkene 10-nitro-oleic acid (10-NO2-OA). In N27-A dopaminergic cells and in the substantia nigra pars compacta of rats, 10-NO2-OA activated Nrf2-regulated gene expression and inhibited NOX2 and LRRK2 hyperactivation, oxidative stress, microglial activation, α-synuclein modification, and downstream mitochondrial import impairment. These data reveal broad neuroprotective actions of 10-NO2-OA in a sub-acute model of PD and motivate more chronic studies in rodents and primates. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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