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Anti-inflammatory reprogramming of microglia cells by metabolic modulators to counteract neurodegeneration; a new
Ilaria Piano1, Arianna Votta2, Patrizia Colucci2
1Department of Pharmacy, University of Pisa, Pisa, Italy.
Abstract:
Microglia chronic activation is a hallmark of several neurodegenerative diseases, including the retinal ones, possibly contributing to their etiopathogenesis. However, some microglia sub-populations have anti-inflammatory and neuroprotective functions, thus making arduous deciphering the role of these cells in neurodegeneration. Since it has been proposed that functionally different microglia subsets also rely on different metabolic routes, we hypothesized that modulating microglia metabolism might be a tool to enhance their anti-inflammatory features. This would have a preventive and therapeutic potential in counteracting neurodegenerative diseases. For this purpose, we tested various molecules known to act on cell metabolism, and we revealed the anti-inflammatory effect of the FDA-approved piperazine derivative Ranolazine on microglia cells, while confirming the one of the flavonoids Quercetin and Naringenin, both in vitro and in vivo. We also demonstrated the synergistic anti-inflammatory effect of Quercetin and Idebenone, and the ability of Ranolazine, Quercetin and Naringenin to counteract the neurotoxic effect of LPS-activated microglia on 661W neuronal cells. Overall, these data suggest that using the selected molecules -also in combination therapies- might represent a valuable approach to reduce inflammation and neurodegeneration while avoiding long term side effects of corticosteroids.
Insights
Modulating microglia metabolism with Ranolazine, Quercetin, and Naringenin shows anti-inflammatory effects. These compounds may offer a novel therapeutic strategy for neurodegenerative diseases by reducing inflammation and neurotoxicity.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Chronic activation of microglia is implicated in neurodegenerative diseases, including retinal ones.
- The dual role of microglia (pro- and anti-inflammatory) complicates understanding their contribution to neurodegeneration.
- Metabolic pathways may differ between microglia subsets, suggesting metabolism as a therapeutic target.
Purpose of the Study:
- To investigate if modulating microglia metabolism can enhance their anti-inflammatory and neuroprotective functions.
- To identify specific molecules with the potential to counteract neuroinflammation and neurodegeneration.
- To explore combination therapies for enhanced efficacy.
Main Methods:
- Tested various metabolism-targeting molecules on microglia cells.
- Evaluated anti-inflammatory effects of Ranolazine, Quercetin, and Naringenin in vitro and in vivo.
- Assessed the neuroprotective effects against lipopolysaccharide (LPS)-activated microglia on neuronal cells.
Main Results:
- Ranolazine, Quercetin, and Naringenin demonstrated anti-inflammatory effects on microglia.
- Quercetin and Idebenone showed synergistic anti-inflammatory activity.
- Ranolazine, Quercetin, and Naringenin protected neuronal cells from LPS-induced neurotoxicity.
Conclusions:
- Modulating microglia metabolism offers a promising therapeutic avenue for neurodegenerative diseases.
- Selected molecules, including Ranolazine, Quercetin, and Naringenin, exhibit anti-inflammatory and neuroprotective properties.
- Combination therapies with these agents may reduce inflammation and neurodegeneration with fewer side effects than corticosteroids.
