Metformin inhibition of mitochondrial ATP and DNA synthesis abrogates NLRP3 inflammasome activation and pulmonary inflammation
Xian H, Liu Y, Rundberg Nilsson A, Gatchalian R, Crother T, Tourtellotte W, Zhang Y, Aleman-Muench G, Lewis G, Chen W, Kang S, Luevanos M, Trudler D, Lipton S, Soroosh P, Teijaro J, de la Torre J, Arditi M, Karin M, Sanchez-Lopez E. Metformin inhibition of mitochondrial ATP and DNA synthesis abrogates NLRP3 inflammasome activation and pulmonary inflammation. Immunity 2021, 54: 1463-1477.e11. PMID: 34115964, PMCID: PMC8189765, DOI: 10.1016/j.immuni.2021.05.004.Peer-Reviewed Original ResearchConceptsAcute respiratory distress syndromeInflammasome activationSARS-CoV-2-induced acute respiratory distress syndromeMyeloid-specific ablationSevere COVID-19Anti-diabetic medicationsAnti-inflammatory effectsRespiratory distress syndromeIL-6 secretionNLRP3 inflammasome activationHigh mortality rateCOVID-19 lungsInhibition of ATPDistress syndromePulmonary inflammationIL-6Inflammatory conditionsMetformin inhibitionMetformin inhibitsARDS severityNF-κBNLRP3 ligandsMortality rateAlveolar macrophagesDNA synthesisSoluble α-synuclein–antibody complexes activate the NLRP3 inflammasome in hiPSC-derived microglia
Trudler D, Nazor K, Eisele Y, Grabauskas T, Dolatabadi N, Parker J, Sultan A, Zhong Z, Goodwin M, Levites Y, Golde T, Kelly J, Sierks M, Schork N, Karin M, Ambasudhan R, Lipton S. Soluble α-synuclein–antibody complexes activate the NLRP3 inflammasome in hiPSC-derived microglia. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2025847118. PMID: 33833060, PMCID: PMC8054017, DOI: 10.1073/pnas.2025847118.Peer-Reviewed Original ResearchConceptsHuman microgliaLike receptor family pyrinFibrillar αSynA9 dopaminergic neuronsInterleukin-1β secretionCaspase-1 activationMicroglial activationFamily pyrinAntibody therapyNeuronal deathParkinson's diseaseMicrogliaMouse brainΑ-synucleinDual stimulationMitochondrial damageΑSynAntibodiesInflammationNLRP3Cognate antibodiesHuman brainDiseaseNeuronsStem cells