Publications by authors named "Elisabetta Bonfanti"
Article Synopsis
- - Microglia and macrophages produce extracellular vesicles (EVs) that can affect the development of myelin lesions, with microglial EVs supporting oligodendrocyte precursor cell (OPC) differentiation, while the effect of macrophage EVs is less clear.
- - Research showed that EVs from macrophages, especially those in an inflammatory state, do not aid OPC differentiation and actually inhibit it, but their lipid content can still promote OPC maturation similar to microglial EVs.
- - Key promyelinating endocannabinoids (like anandamide) were found in EVs from both cell types, indicating a critical role for these endocannabinoids in OPC maturation and suggesting potential targets for enhancing myelin repair
Article Synopsis
- Research highlights the potential of promoting new myelinating oligodendrocytes to aid recovery after stroke by studying microglia and macrophage roles.
- Using GPR17-expressing OPCs in a mouse model, findings show that early activation of these immune cells supports OPC reactions and reduces myelin damage, but they eventually become dysfunctional over time.
- Infusing microglial-derived extracellular vesicles can restore immune cell function and enhance OPC maturation, improving neurological outcomes, with tmTNF identified as a key factor in OPC differentiation.
Article Synopsis
- The GPR17 receptor, found on oligodendroglial precursors, is a promising target for developing treatments that promote myelin production in multiple sclerosis (MS).
- Researchers screened over 1,000,000 compounds to find selective agents that can activate GPR17, going through a multi-step testing and refinement process.
- One promising compound, galinex, was shown to significantly delay the onset of experimental autoimmune encephalomyelitis (EAE), supporting the effectiveness of their drug discovery approach for discovering new MS treatments.
Article Synopsis
- Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that leads to the loss of motor neurons, closely associated with issues in oligodendrocytes and their precursors, which are crucial for repairing nerve insulation (myelin).
- The function of GPR17, a receptor linked to oligodendrocyte maturation, was studied in ALS, revealing that its levels significantly rise in the spinal cords of ALS mouse models, correlating with oligodendrocyte degeneration.
- Treatment with the GPR17 antagonist montelukast improved the differentiation of oligodendrocyte precursor cells in SOD1 ALS mice, suggesting new therapeutic strategies for ALS.
Article Synopsis
- The study examined surface plasmon resonance (SPR) spectroscopy to measure real-time ligand-binding affinities and kinetic parameters for GPR17, a GPCR relevant to treating demyelinating diseases.
- It successfully captured the receptor on a sensor chip, retaining its binding activity for over 24 hours and allowing for reuse after mild regeneration.
- The findings, including binding constants and functional assays, revealed important insights into how GPR17 interacts with ligands like Cangrelor and Asinex 1, with Asinex 1 identified as an effective agonist promoting cell maturation.
Article Synopsis
- - Microglia, the brain's immune cells, can either promote or inhibit the repair of myelin, a protective layer around nerve fibers, in conditions like multiple sclerosis, depending on their activation state.
- - The study found that extracellular vesicles (EVs) from pro-inflammatory microglia hindered myelin repair, while those from microglia working with mesenchymal stem cells promoted the recruitment of oligodendrocyte precursor cells (OPCs) for remyelination.
- - The research also revealed that astrocytes (another type of brain cell) can be negatively affected by pro-inflammatory EVs, which disrupt OPC maturation, suggesting that EVs have complex roles in signaling and may hold potential for new treatments for
Stroke is one of the main causes of death, neurological dysfunctions or disability in elderly. Neuroprotective drugs have been proposed to improve long-term recovery after stroke, but failed to reach clinical effectiveness. Hence, recent studies suggested that restorative therapies should combine neuroprotection and remyelination.
View Article and Find Full Text PDFArticle Synopsis
- Oligodendrocyte loss can cause issues with thinking and movement, prompting the need for therapies that can either enhance the body's own precursors or use transplanted oligodendrocytes.
- A new method has been developed to extract and expand oligodendrocyte lineage cells from adult rat meninges, yielding about 10 million cells from just a small tissue sample in about 4 weeks.
- These meningeal-derived cells not only show characteristics of mature oligodendrocytes but also have potential to remyelinate damaged areas in the spinal cord, making them a promising option for treating demyelinating diseases.
Following stroke-induced neuronal damage, quiescent oligodendrocyte precursors (OPCs) are activated to proliferate and later to differentiate to myelin-producing cells. GPR17, a receptor transiently expressed on early OPCs, has emerged as a target to implement stroke repair through stimulation of OPC maturation. However, being GPR17 completely downregulated in myelin-producing oligodendrocytes, its actual role in determining the final fate of OPCs after cerebral ischemia is still uncertain.
View Article and Find Full Text PDFIn the adult brain NG2-glia continuously generate mature, myelinating oligodendrocytes. To which extent the differentiation process is common to all NG2-glia and whether distinct pools are recruited for repair under physiological and pathological conditions still needs clarification. Here, we aimed at investigating the differentiation potential of adult NG2-glia that specifically express the G-protein coupled receptor 17 (GPR17), a membrane receptor that regulates the differentiation of these cells at postnatal stages.
View Article and Find Full Text PDFArticle Synopsis
- * The study identifies Murine double minute 2 (Mdm2) as a key player that regulates the function of GRK2, impacting GPR17's down-regulation and the maturation of oligodendrocyte precursor cells.
- * Treatments with rapamycin and Nutlin-3 highlighted Mdm2's role in linking mTOR signaling with GRK2, revealing a new mechanism that affects myelination processes.
Article Synopsis
- The differentiation of oligodendrocyte-precursor cells (OPCs) is affected by the dysfunctional regulation of GPR17, which plays a role in multiple sclerosis progression.
- The study investigates how the GRK-β arrestin system influences GPR17's function, particularly how different GRK isoforms are activated by purinergic and cysLT ligands during OPC maturation.
- The findings reveal that GRK2 is essential for cysLT-induced OPC maturation, while GRK5 is specifically recruited by purinergic ligands, indicating that different ligands activate distinct signaling pathways that ultimately contribute to OPC differentiation.
In the developing and mature central nervous system, NG2 expressing cells comprise a population of cycling oligodendrocyte progenitor cells (OPCs) that differentiate into mature, myelinating oligodendrocytes (OLGs). OPCs are also characterized by high motility and respond to injury by migrating into the lesioned area to support remyelination. K(+) currents in OPCs are developmentally regulated during differentiation.
View Article and Find Full Text PDF