Rodríguez-Gómez, José A.Kavanagh, EdelEngskog-Vlachos, PinelopiEngskog, Mikael K. R.Herrera, Antonio J.Espinosa-Oliva, Ana M.Joseph, BertrandHajji, NabilVenero, José L.Burguillos, Miguel A.2022-04-282022-04-282020-07-17Rodríguez-Gómez JA, Kavanagh E, Engskog-Vlachos P, Engskog MKR, Herrera AJ, Espinosa-Oliva AM, et al. Microglia: Agents of the CNS Pro-Inflammatory Response. Cells. 2020 Jul 17;9(7):1717http://hdl.handle.net/10668/3592The pro-inflammatory immune response driven by microglia is a key contributor to the pathogenesis of several neurodegenerative diseases. Though the research of microglia spans over a century, the last two decades have increased our understanding exponentially. Here, we discuss the phenotypic transformation from homeostatic microglia towards reactive microglia, initiated by specific ligand binding to pattern recognition receptors including toll-like receptor-4 (TLR4) or triggering receptors expressed on myeloid cells-2 (TREM2), as well as pro-inflammatory signaling pathways triggered such as the caspase-mediated immune response. Additionally, new research disciplines such as epigenetics and immunometabolism have provided us with a more holistic view of how changes in DNA methylation, microRNAs, and the metabolome may influence the pro-inflammatory response. This review aimed to discuss our current knowledge of pro-inflammatory microglia from different angles, including recent research highlights such as the role of exosomes in spreading neuroinflammation and emerging techniques in microglia research including positron emission tomography (PET) scanning and the use of human microglia generated from induced pluripotent stem cells (iPSCs). Finally, we also discuss current thoughts on the impact of pro-inflammatory microglia in neurodegenerative diseases.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/MicrogliaInflammationTLR4TREM2CaspasesEpigeneticsmetabolomicsiPSCsMicroglíaInflamaciónReceptor Toll-Like 4CaspasasEpigenómicaMetabolómicaCélulas madre pluripotentes inducidasMedical Subject Headings::Organisms::Eukaryota::AnimalsMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intracellular Signaling Peptides and Proteins::Apoptosis Regulatory Proteins::CaspasesMedical Subject Headings::Anatomy::Nervous System::Central Nervous SystemMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation::Epigenesis, GeneticMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::InflammationMedical Subject Headings::Anatomy::Cells::Neuroglia::MicrogliaMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Models, Theoretical::Models, BiologicalMedical Subject Headings::Anatomy::Cells::Stem Cells::Pluripotent Stem Cells::Induced Pluripotent Stem CellsMedical Subject Headings::Disciplines and Occupations::Natural Science Disciplines::Biological Science Disciplines::Biology::Genetics::Genomics::Epigenomicsreview article32709045open access10.3390/cells90717172073-4409PMC7407646