Metabolic Profiling Reveals a Glycolytic Shift and an IRG1/Itaconate/NF2L2 Axis Regulating Neurotoxic Oxidative Stress in Inflammatory Microglia.

Polar metabolic profiling, as well as bioenergetic assays, were used to characterize microglial responses to lipopolysaccharide, which induces a pro-inflammatory state, and interleukin-4, which is associated with an anti-inflammatory phenotype. BV2 microglial cells and primary microglia were used for these investigations. Results revealed that lipopolysaccharide-treated microglia exhibited an increased aerobic glycolytic activity measured by extracellular flux analysis, accompanied by increased levels of endogenous itaconate, a metabolite produced by the IRG1 enzyme.

Age-associated microglial transcriptome leads to diminished immunogenicity and dysregulation of MCT4 and P2RY12/P2RY13 related functions.

The aging process is marked by a time-dependent deterioration in cellular functions, particularly the immune and neural systems. Understanding the phenotype acquisition of microglia, the sentinel immune cells of the brain, is crucial for understanding the nature of age-related neurological diseases. However, the specific phenotype adopted by microglia during aging remains a subject of debate and is contingent on the chosen experimental model.

Bi-allelic NRXN1α deletion in microglia derived from iPSC of an autistic patient increases interleukin-6 production and impairs supporting function on neuronal networking.

Autism spectrum disorder (ASD) is a set of heterogeneous neurodevelopmental conditions, with a highly diverse genetic hereditary component, including altered neuronal circuits, that has an impact on communication skills and behaviours of the affected individuals. Beside the recognised role of neuronal alterations, perturbations of microglia and the associated neuroinflammatory processes have emerged as credible contributors to aetiology and physiopathology of ASD. Mutations in NRXN1, a member of the neurexin family of cell-surface receptors that bind neuroligin, have been associated to ASD.

ID2-ETS2 axis regulates the transcriptional acquisition of pro-tumoral microglia phenotype in glioma.

Glioblastoma is a highly aggressive brain tumour that creates an immunosuppressive microenvironment. Microglia, the brain's resident immune cells, play a crucial role in this environment. Glioblastoma cells can reprogramme microglia to create a supportive niche that promotes tumour growth.

Proteome integral solubility alteration high-throughput proteomics assay identifies Collectin-12 as a non-apoptotic microglial caspase-3 substrate.

Caspases are a family of proteins mostly known for their role in the activation of the apoptotic pathway leading to cell death. In the last decade, caspases have been found to fulfill other tasks regulating the cell phenotype independently to cell death. Microglia are the immune cells of the brain responsible for the maintenance of physiological brain functions but can also be involved in disease progression when overactivated.

Semisynthetic quercetin-quinone mitigates BV-2 microglia activation through modulation of Nrf2 pathway.

During brain ageing, microglia, the resident immune cells of the CNS, are immunologically activated and contribute to neuroinflammation, a vicious cycle that supports development of neurological disorders. Therapeutic approaches focus mainly on downregulation of their pro-inflammatory activated state that is associated with health benefits. Electrophilic compounds, such as natural quinones and their reduced pro-electrophilic precursors, flavonoids, represent a wide group of diverse substances with important biological effects.

Protective Effect of Semisynthetic and Natural Flavonoid on Aged Rat Microglia-enriched Cultures.

The ROS-mediated lysosomal dysfunction and coinciding deterioration of mitochondrial function are thought to be the prominent mechanisms responsible for aging. Microglia, the resident macrophages in the central nervous system, were postulated to belong to the major targets vulnerable to these detrimental processes, acting as principal drivers in brain aging. The present study investigated the potential protective effect of the semisynthetic flavonoid 3'-O-(3-chloropivaloyl) quercetin (CPQ) and quercetin (Q) on microglia-enriched mixed brain cultures (MBCs) established from aged Wistar rats.

Pyridoindole SMe1EC2 as cognition enhancer in ageing-related cognitive decline.

Synthetic pyridoindole-type substances derived from the lead compound stobadine represent promising agents in treatment of a range of pathologies including neurological disorders. The beneficial biological effects were suggested to be likely associated with their capacity to ameliorate oxidative damage. In our study, the effect of supplementation with the derivative of stobadine, SMe1EC2, on ageing-related cognitive decline in rats was investigated.

Modulation of BV-2 microglia functions by novel quercetin pivaloyl ester.

Chronic inflammation in brain plays a critical role in major neurodegenerative diseases such as Alzheimer's, Parkinson's disease, stroke or multiple sclerosis. Microglia, resident macrophages and intristinc components of CNS, appear to be main effectors in this pathological process. Quercetin, a naturally occurring flavonoid, was proven to downregulate inflammatory genes in microglia.