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Brain Sciences
Par Tatiana P. Gerasimova, Ekaterina V. Novosadova, Ekaterina A. Stepanenko et 4 autres.
Contenu en anglais
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Neuroinflammation and neurodegeneration are closely linked in Parkinson’s disease (PD). Specialized pro-resolving mediators (SPMs) are of interest as potential therapeutic agents for PD because they promote the resolution of inflammation.
We investigated whether PARK2 mutations are associated with cell-type-specific patterns of SPM receptor expression by comparing neuronal and glial cultures derived from induced pluripotent stem cells (iPSCs) of PD patients carrying different PARK2 mutations with corresponding cultures from healthy donors (HDs), using real-time PCR and Western blotting.
The resolvin E1 receptors, BLT1 and CHEMR23, and the resolvin D1 (RvD1) receptors, GPR32 and FPR2, were detected at both the mRNA and protein levels in PARK2-mutant neurons and glia. Compared with HD cultures, mutant neurons had significantly higher CHEMR23 protein levels despite similar CHEMR23 mRNA levels, whereas no statistically detectable differences in the expression of any of the four receptors were found in glia. Receptor profiles also appeared to differ between cells carrying PARK2 mutations and those carrying mutations in other genes (GBA1, LRRK2). PARK2-mutant neurons showed lower levels of several inflammatory markers than HD neurons, in contrast to the pro-inflammatory profile previously reported in PARK2-mutant glia. A pilot experiment with glial cultures derived from one cell line per group suggested that in the presence of TNFα, RvD1 may reduce IL-6 secretion and increase cellular metabolic activity in PARK2-mutant glia, with responses that appeared to differ from those observed in HD glia.
The presence of resolvin receptors in PARK2-mutant neurons and glia, together with elevated CHEMR23 protein levels in mutant neurons compared with HD neurons, provides a basis for further investigation of resolvin signaling in PARK2-associated PD. However, the relationship between receptor expression and functional responses to resolvins remains to be established. The contrasting inflammatory profiles of neurons and glia suggest that PARK2-mutant glial cultures may be particularly relevant for investigating the anti-inflammatory effects of resolvins.
Cell-type- and genetic-background-associated differences in receptor expression should be considered when developing resolvin-based therapeutic approaches for PD. Further studies are needed to assess the potential anti-inflammatory effects of RvD1 on glial cells in genetic forms of the disease.
Publié dans Brain Sciences. Le résumé est reproduit tel qu’il a été publié et reste l’œuvre de ses auteurs ; lisez l’article complet à la source.
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