SCIENCE@home

Neuroprotective actions of a fatty acid nitroalkene in Parkinson’s disease

R. Di Maio,Matthew T. Keeney,Veronika Cechova,A. Mortimer,Ahssan Sekandari,Pascal Rowart,J. Greenamyre,B. Freeman,M. Fazzari

Published 2023 in npj Parkinson's Disease

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-NO_2-OA). In N27-A dopaminergic cells and in the substantia nigra pars compacta of rats, 10-NO_2-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-NO_2-OA in a sub-acute model of PD and motivate more chronic studies in rodents and primates.

PUBLICATION RECORD

CITATION MAP

EXTRACTION MAP

CLAIMS

  • No claims are published for this paper.

CONCEPTS

  • No concepts are published for this paper.

REFERENCES

Showing 1-88 of 88 references · Page 1 of 1

CITED BY

Showing 1-11 of 11 citing papers · Page 1 of 1