{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T18:43:04Z","timestamp":1793126584995,"version":"4.5.0"},"reference-count":125,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,5,31]],"date-time":"2023-05-31T00:00:00Z","timestamp":1685491200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["R01DA054826"],"award-info":[{"award-number":["R01DA054826"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>During the last decade, substance use disorders (SUDs) have been increasingly recognized as neuroinflammation-related brain diseases. Various types of abused drugs (cocaine, methamphetamine, alcohol, opiate-like drugs, marijuana, etc.) can modulate the activation status of microglia and neuroinflammation levels which are involved in the pathogenesis of SUDs. Several neuroimmune signaling pathways, including TLR\/NF-\u043aB, reactive oxygen species, mitochondria dysfunction, as well as autophagy defection, etc., have been implicated in promoting SUDs. Recently, inflammasome-mediated signaling has been identified as playing critical roles in the microglia activation induced by abused drugs. Among the family of inflammasomes, NOD-, LRR-, and pyrin-domain-containing protein 3 (NLRP3) serves the primary research target due to its abundant expression in microglia. NLRP3 has the capability of integrating multiple external and internal inputs and coordinately determining the intensity of microglia activation under various pathological conditions. Here, we summarize the effects of abused drugs on NLRP3 inflammasomes, as well as others, if any. The research on this topic is still at an infant stage; however, the readily available findings suggest that NLRP3 inflammasome could be a common downstream effector stimulated by various types of abused drugs and play critical roles in determining abused-drug-mediated biological effects through enhancing glia\u2013neuron communications. NLRP3 inflammasome might serve as a novel target for ameliorating the development of SUDs.<\/jats:p>","DOI":"10.3390\/biom13060922","type":"journal-article","created":{"date-parts":[[2023,6,1]],"date-time":"2023-06-01T03:06:00Z","timestamp":1685588760000},"page":"922","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Microglia NLRP3 Inflammasome and Neuroimmune Signaling in Substance Use Disorders"],"prefix":"10.3390","volume":"13","author":[{"given":"Ming-Lei","family":"Guo","sequence":"first","affiliation":[{"name":"Drug Addiction Laboratory, Department of Pathology and Anatomy, Eastern Virginia Medical School, Norfolk, VA 23507, USA"},{"name":"Center for Integrative Neuroscience and Inflammatory Diseases, Eastern Virginia Medical School, Norfolk, VA 23507, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6005-0673","authenticated-orcid":false,"given":"Soheil Kazemi","family":"Roodsari","sequence":"additional","affiliation":[{"name":"Drug Addiction Laboratory, Department of Pathology and Anatomy, Eastern Virginia Medical School, Norfolk, VA 23507, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Cheng","sequence":"additional","affiliation":[{"name":"Drug Addiction Laboratory, Department of Pathology and Anatomy, Eastern Virginia Medical School, Norfolk, VA 23507, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachael Elizabeth","family":"Dempsey","sequence":"additional","affiliation":[{"name":"Drug Addiction Laboratory, Department of Pathology and Anatomy, Eastern Virginia Medical School, Norfolk, VA 23507, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhui","family":"Hu","sequence":"additional","affiliation":[{"name":"Center for Metabolic Disease Research, Department of Pathology and Laboratory Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/0306-4522(90)90229-W","article-title":"Heterogeneity in the distribution and morphology of microglia in the normal adult mouse brain","volume":"39","author":"Lawson","year":"1990","journal-title":"Neuroscience"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1007\/s004010000284","article-title":"Local distribution of microglia in the normal adult human central nervous system differs by up to one order of magnitude","volume":"101","author":"Mittelbronn","year":"2001","journal-title":"Acta Neuropathol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1016\/j.neurobiolaging.2007.04.013","article-title":"Neocortical glial cell numbers in human brains","volume":"29","author":"Pelvig","year":"2008","journal-title":"Neurobiol. Aging"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.cell.2019.08.053","article-title":"Microglia Biology: One Century of Evolving Concepts","volume":"179","author":"Prinz","year":"2019","journal-title":"Cell"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.cell.2014.06.008","article-title":"Sublime microglia: Expanding roles for the guardians of the CNS","volume":"158","author":"Salter","year":"2014","journal-title":"Cell"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1038\/s41593-018-0145-x","article-title":"Microglial immune checkpoint mechanisms","volume":"21","author":"Deczkowska","year":"2018","journal-title":"Nat. Neurosci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1038\/s41593-018-0242-x","article-title":"Microglia in neurodegeneration","volume":"21","author":"Hickman","year":"2018","journal-title":"Nat. Neurosci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"854","DOI":"10.2174\/1567205020666230203112351","article-title":"Roles of Microglia in AD Pathology","volume":"19","author":"Rong","year":"2023","journal-title":"Curr. Alzheimer Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s13073-023-01155-w","article-title":"The neuroimmune axis of Alzheimer\u2019s disease","volume":"15","author":"Jorfi","year":"2023","journal-title":"Genome Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/s12974-023-02723-y","article-title":"The reciprocal interactions between microglia and T cells in Parkinson\u2019s disease: A double-edged sword","volume":"20","author":"Xu","year":"2023","journal-title":"J. Neuroinflamm."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1039780","DOI":"10.3389\/fnagi.2022.1039780","article-title":"The role of microglial autophagy in Parkinson\u2019s disease","volume":"14","author":"Zhu","year":"2022","journal-title":"Front. Aging Neurosci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1002\/dneu.22905","article-title":"Microglia in motor neuron disease: Signaling evidence from last 10 years","volume":"82","author":"Wang","year":"2022","journal-title":"Dev. Neurobiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/j.neubiorev.2019.09.007","article-title":"A potential role for microglia in stress- and drug-induced plasticity in the nucleus accumbens: A mechanism for stress-induced vulnerability to substance use disorder","volume":"107","author":"McGrath","year":"2019","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.conb.2019.02.010","article-title":"Glial regulation of synaptic function in models of addiction","volume":"57","author":"Stellwagen","year":"2019","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1038\/nature10759","article-title":"Inflammasomes in health and disease","volume":"481","author":"Strowig","year":"2012","journal-title":"Nature"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1109938","DOI":"10.3389\/fimmu.2022.1109938","article-title":"The mechanism of NLRP3 inflammasome activation and its pharmacological inhibitors","volume":"13","author":"Zhan","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1038\/s41583-018-0057-5","article-title":"Microglial signatures and their role in health and disease","volume":"19","author":"Butovsky","year":"2018","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.neuron.2017.06.020","article-title":"Local Cues Establish and Maintain Region-Specific Phenotypes of Basal Ganglia Microglia","volume":"95","author":"Schuebel","year":"2017","journal-title":"Neuron"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.neuron.2020.11.007","article-title":"Shaping Neuronal Fate: Functional Heterogeneity of Direct Microglia-Neuron Interactions","volume":"109","author":"Cserep","year":"2021","journal-title":"Neuron"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1038\/nn.4222","article-title":"Microglial brain region-dependent diversity and selective regional sensitivities to aging","volume":"19","author":"Grabert","year":"2016","journal-title":"Nat. Neurosci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1186\/s13024-022-00584-2","article-title":"Single-cell microglial transcriptomics during demyelination defines a microglial state required for lytic carcass clearance","volume":"17","author":"Zia","year":"2022","journal-title":"Mol. Neurodegener."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"235","DOI":"10.3389\/fnins.2019.00235","article-title":"RNA Sequencing Reveals Small and Variable Contributions of Infectious Agents to Transcriptomes of Postmortem Nervous Tissues from Amyotrophic Lateral Sclerosis, Alzheimer\u2019s Disease and Parkinson\u2019s Disease Subjects, and Increased Expression of Genes From Disease-Activated Microglia","volume":"13","author":"Bennett","year":"2019","journal-title":"Front. Neurosci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"896852","DOI":"10.3389\/fnagi.2022.896852","article-title":"Functional and Phenotypic Diversity of Microglia: Implication for Microglia-Based Therapies for Alzheimer\u2019s Disease","volume":"14","author":"Xu","year":"2022","journal-title":"Front. Aging Neurosci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1016\/j.cell.2017.05.018","article-title":"A Unique Microglia Type Associated with Restricting Development of Alzheimer\u2019s Disease","volume":"169","author":"Spinrad","year":"2017","journal-title":"Cell"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1016\/j.immuni.2017.08.008","article-title":"The TREM2-APOE Pathway Drives the Transcriptional Phenotype of Dysfunctional Microglia in Neurodegenerative Diseases","volume":"47","author":"Krasemann","year":"2017","journal-title":"Immunity"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.neuron.2018.12.006","article-title":"Developmental Heterogeneity of Microglia and Brain Myeloid Cells Revealed by Deep Single-Cell RNA Sequencing","volume":"101","author":"Li","year":"2019","journal-title":"Neuron"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1186\/s13041-022-00960-5","article-title":"Toll-like receptors and their role in neuropathic pain and migraine","volume":"15","author":"Liu","year":"2022","journal-title":"Mol. Brain"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"121","DOI":"10.3389\/fncel.2014.00121","article-title":"Fractalkine\/CX3CR1 signaling during neuropathic pain","volume":"8","author":"Clark","year":"2014","journal-title":"Front. Cell. Neurosci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1007\/s11481-007-9075-1","article-title":"CD200-CD200R regulation of microglia activation in the pathogenesis of Parkinson\u2019s disease","volume":"2","author":"Wang","year":"2007","journal-title":"J. Neuroimmune Pharmacol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1146\/annurev-immunol-081022-021207","article-title":"Structural Mechanisms of NLRP3 Inflammasome Assembly and Activation","volume":"41","author":"Fu","year":"2022","journal-title":"Annu. Rev. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.pbb.2018.12.007","article-title":"Neuroimmune signaling in alcohol use disorder","volume":"177","author":"Erickson","year":"2019","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/B978-0-12-801284-0.00001-4","article-title":"Neuroimmune mechanisms of alcohol and drug addiction","volume":"118","author":"Cui","year":"2014","journal-title":"Int. Rev. Neurobiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1017\/neu.2014.24","article-title":"Neuroinflammation as a possible link between cannabinoids and addiction","volume":"26","author":"Rodrigues","year":"2014","journal-title":"Acta Neuropsychiatr."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.drugalcdep.2015.11.024","article-title":"Cocaine abuse and effects in the serum levels of cytokines IL-6 and IL-10","volume":"158","author":"Moreira","year":"2016","journal-title":"Drug Alcohol Depend."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.neulet.2013.03.045","article-title":"Peripheral toxicity in crack cocaine use disorders","volume":"544","author":"Narvaez","year":"2013","journal-title":"Neurosci. Lett."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"650785","DOI":"10.3389\/fnins.2021.650785","article-title":"Neuroimmune Mechanisms as Novel Treatment Targets for Substance Use Disorders and Associated Comorbidities","volume":"15","author":"Namba","year":"2021","journal-title":"Front. Neurosci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1007\/s40263-020-00721-9","article-title":"Potential of Glial Cell Modulators in the Management of Substance Use Disorders","volume":"34","author":"Jones","year":"2020","journal-title":"CNS Drugs"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/s12974-016-0501-2","article-title":"Cocaine-mediated induction of microglial activation involves the ER stress-TLR2 axis","volume":"13","author":"Liao","year":"2016","journal-title":"J. Neuroinflamm."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1007\/s10571-022-01223-6","article-title":"Neuroinflammatory Response in Reward-Associated Psychostimulants and Opioids: A Review","volume":"43","author":"Chavoshinezhad","year":"2023","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1525","DOI":"10.1038\/mp.2014.177","article-title":"DAT isn\u2019t all that: Cocaine reward and reinforcement require Toll-like receptor 4 signaling","volume":"20","author":"Northcutt","year":"2015","journal-title":"Mol. Psychiatry"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3196","DOI":"10.1007\/s12035-017-0584-5","article-title":"Cocaine-Mediated Downregulation of miR-124 Activates Microglia by Targeting KLF4 and TLR4 Signaling","volume":"55","author":"Periyasamy","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1080\/15592294.2016.1232233","article-title":"Cocaine-mediated downregulation of microglial miR-124 expression involves promoter DNA methylation","volume":"11","author":"Guo","year":"2016","journal-title":"Epigenetics"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1080\/15548627.2015.1052205","article-title":"Cocaine-mediated microglial activation involves the ER stress-autophagy axis","volume":"11","author":"Guo","year":"2015","journal-title":"Autophagy"},{"key":"ref_44","first-page":"165","article-title":"Inflammasome in drug abuse","volume":"9","author":"Xu","year":"2017","journal-title":"Int. J. Physiol. Pathophysiol. Pharmacol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"27864","DOI":"10.1038\/srep27864","article-title":"Effect of Cocaine on HIV Infection and Inflammasome Gene Expression Profile in HIV Infected Macrophages","volume":"6","author":"Atluri","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2215","DOI":"10.1007\/s12035-020-02184-x","article-title":"NLRP3 Inflammasome Blockade Reduces Cocaine-Induced Microglial Activation and Neuroinflammation","volume":"58","author":"Chivero","year":"2021","journal-title":"Mol. Neurobiol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Guo, M.L., Chivero, E.T., Callen, S.E., and Buch, S. (2021). NLRP3 Inflammasome Is Involved in Cocaine-Mediated Potentiation on Behavioral Changes in CX3CR1-Deficient Mice. J. Pers. Med., 11.","DOI":"10.3390\/jpm11100963"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"120564","DOI":"10.1016\/j.lfs.2022.120564","article-title":"CX3CL1 inhibits NLRP3 inflammasome-induced microglial pyroptosis and improves neuronal function in mice with experimentally-induced ischemic stroke","volume":"300","author":"Ge","year":"2022","journal-title":"Life Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"108089","DOI":"10.1016\/j.drugalcdep.2020.108089","article-title":"Trends in characteristics of individuals who use methamphetamine in the United States, 2015\u20132018","volume":"213","author":"Palamar","year":"2020","journal-title":"Drug Alcohol Depend."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1007\/s11064-021-03513-9","article-title":"The Crosstalk between Neurons and Glia in Methamphetamine-Induced Neuroinflammation","volume":"47","author":"Shi","year":"2022","journal-title":"Neurochem. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"381","DOI":"10.4062\/biomolther.2020.044","article-title":"Methamphetamine-Induced Neuronal Damage: Neurotoxicity and Neuroinflammation","volume":"28","author":"Kim","year":"2020","journal-title":"Biomol. Ther."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1186\/s12974-018-1385-0","article-title":"Methamphetamine neurotoxicity, microglia, and neuroinflammation","volume":"15","author":"Shaerzadeh","year":"2018","journal-title":"J. Neuroinflamm."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"121","DOI":"10.3389\/fphar.2012.00121","article-title":"The effects of psychostimulant drugs on blood brain barrier function and neuroinflammation","volume":"3","author":"Kousik","year":"2012","journal-title":"Front. Pharmacol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1038\/nm.3111","article-title":"Peli1 promotes microglia-mediated CNS inflammation by regulating Traf3 degradation","volume":"19","author":"Xiao","year":"2013","journal-title":"Nat. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"398","DOI":"10.3389\/fnmol.2017.00398","article-title":"Peli1 Contributions in Microglial Activation, Neuroinflammatory Responses and Neurological Deficits Following Experimental Subarachnoid Hemorrhage","volume":"10","author":"Huang","year":"2017","journal-title":"Front. Mol. Neurosci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.toxlet.2020.07.028","article-title":"Methamphetamine induced neuroinflammation in mouse brain and microglial cell line BV2: Roles of the TLR4\/TRIF\/Peli1 signaling axis","volume":"333","author":"Yang","year":"2020","journal-title":"Toxicol. Lett."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1007\/s12640-019-00156-1","article-title":"Protective Effects of Melatonin on Methamphetamine-Induced Blood-Brain Barrier Dysfunction in Rat Model","volume":"37","author":"Namyen","year":"2020","journal-title":"Neurotox. Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.taap.2019.03.019","article-title":"MiR-142a-3p and miR-155-5p reduce methamphetamine-induced inflammation: Role of the target protein Peli1","volume":"370","author":"Yu","year":"2019","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.expneurol.2013.04.009","article-title":"SN79, a sigma receptor ligand, blocks methamphetamine-induced microglial activation and cytokine upregulation","volume":"247","author":"Robson","year":"2013","journal-title":"Exp. Neurol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1007\/s11481-018-9780-y","article-title":"Inflammasome Activation by Methamphetamine Potentiates Lipopolysaccharide Stimulation of IL-1beta Production in Microglia","volume":"13","author":"Xu","year":"2018","journal-title":"J. Neuroimmune Pharmacol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.toxlet.2018.10.020","article-title":"Involvement of NLRP3 inflammasome in methamphetamine-induced microglial activation through miR-143\/PUMA axis","volume":"301","author":"Du","year":"2019","journal-title":"Toxicol. Lett."},{"key":"ref_62","first-page":"769","article-title":"Nod-like receptor protein 3 and nod-like receptor protein 1 inflammasome activation in the hippocampal region of postmortem methamphetamine chronic user","volume":"120","author":"Mahmoudiasl","year":"2019","journal-title":"Bratisl. Lek. Listy"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"861340","DOI":"10.3389\/fnmol.2022.861340","article-title":"Inflammasome Inhibition Prevents Motor Deficit and Cerebellar Degeneration Induced by Chronic Methamphetamine Administration","volume":"15","author":"Ding","year":"2022","journal-title":"Front. Mol. Neurosci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"8515","DOI":"10.12659\/MSM.920190","article-title":"Methamphetamine Induces Intestinal Inflammatory Injury via Nod-Like Receptor 3 Protein (NLRP3) Inflammasome Overexpression In Vitro and In Vivo","volume":"25","author":"Zhao","year":"2019","journal-title":"Med. Sci. Monit."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"109537","DOI":"10.1016\/j.drugalcdep.2022.109537","article-title":"The effect of the NLRP1 inflammasome on methamphetamine-induced cognitive impairment in rats","volume":"237","author":"Fan","year":"2022","journal-title":"Drug Alcohol Depend."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.neuropharm.2017.01.031","article-title":"The role of neuroimmune signaling in alcoholism","volume":"122","author":"Crews","year":"2017","journal-title":"Neuropharmacology"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/bs.pmbts.2019.06.011","article-title":"Its complicated: The relationship between alcohol and microglia in the search for novel pharmacotherapeutic targets for alcohol use disorders","volume":"167","author":"Melbourne","year":"2019","journal-title":"Prog. Mol. Biol. Transl. Sci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1908","DOI":"10.1111\/acer.14694","article-title":"Primed for addiction: A critical review of the role of microglia in the neurodevelopmental consequences of adolescent alcohol drinking","volume":"45","author":"Melbourne","year":"2021","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Lippai, D., Bala, S., Csak, T., Kurt-Jones, E.A., and Szabo, G. (2013). Chronic alcohol-induced microRNA-155 contributes to neuroinflammation in a TLR4-dependent manner in mice. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0070945"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.bbrc.2014.08.092","article-title":"miR-339-5p inhibits alcohol-induced brain inflammation through regulating NF-kappaB pathway","volume":"452","author":"Zhang","year":"2014","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/s12974-017-0799-4","article-title":"Microglial-derived miRNA let-7 and HMGB1 contribute to ethanol-induced neurotoxicity via TLR7","volume":"14","author":"Coleman","year":"2017","journal-title":"J. Neuroinflamm."},{"key":"ref_72","first-page":"155","article-title":"Epigenetic regulation of MIR-124 under ethanol dependence and withdrawal","volume":"47","author":"Mizuo","year":"2012","journal-title":"Nihon Arukoru Yakubutsu Igakkai Zasshi"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"778456","DOI":"10.3389\/fnbeh.2021.778456","article-title":"Alcohol-Induced Neuroinflammatory Response and Mitochondrial Dysfunction on Aging and Alzheimer\u2019s Disease","volume":"15","author":"Leon","year":"2021","journal-title":"Front. Behav. Neurosci."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"866073","DOI":"10.3389\/fimmu.2022.866073","article-title":"Ethanol Induces Secretion of Proinflammatory Extracellular Vesicles That Inhibit Adult Hippocampal Neurogenesis Through G9a\/GLP-Epigenetic Signaling","volume":"13","author":"Zou","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2260","DOI":"10.1111\/acer.13208","article-title":"Impact of the Innate Immune Response in the Actions of Ethanol on the Central Nervous System","volume":"40","author":"Montesinos","year":"2016","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"8154","DOI":"10.1007\/s12035-018-0957-4","article-title":"NLRs as Helpline in the Brain: Mechanisms and Therapeutic Implications","volume":"55","author":"Singh","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1111\/acer.14272","article-title":"Inhibition of the Inflammasome Signaling Cascade Reduces Alcohol Consumption in Female But Not Male Mice","volume":"44","author":"Lowe","year":"2020","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1016\/j.redox.2017.04.020","article-title":"Mitochondrial ROS induced by chronic ethanol exposure promote hyper-activation of the NLRP3 inflammasome","volume":"12","author":"Hoyt","year":"2017","journal-title":"Redox Biol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1186\/s13041-016-0221-7","article-title":"Ethanol-mediated activation of the NLRP3 inflammasome in iPS cells and iPS cells-derived neural progenitor cells","volume":"9","author":"Halikere","year":"2016","journal-title":"Mol. Brain"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.tox.2015.06.006","article-title":"Ethanol directly induced HMGB1 release through NOX2\/NLRP1 inflammasome in neuronal cells","volume":"334","author":"Wang","year":"2015","journal-title":"Toxicology"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1007\/s11064-015-1760-5","article-title":"Ethanol-Induced TLR4\/NLRP3 Neuroinflammatory Response in Microglial Cells Promotes Leukocyte Infiltration Across the BBB","volume":"41","author":"Guerri","year":"2016","journal-title":"Neurochem. Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1146\/annurev-pathmechdis-032521-102529","article-title":"Role of the Inflammasome in Liver Disease","volume":"17","author":"Szabo","year":"2022","journal-title":"Annu. Rev. Pathol."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Torres, S., Segales, P., Garcia-Ruiz, C., and Fernandez-Checa, J.C. (2022). Mitochondria and the NLRP3 Inflammasome in Alcoholic and Nonalcoholic Steatohepatitis. Cells, 11.","DOI":"10.3390\/cells11091475"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Mainz, R.E., Albers, S., Haque, M., Sonntag, R., Treichel, N.S., Clavel, T., Latz, E., Schneider, K.M., Trautwein, C., and Otto, T. (2022). NLRP6 Inflammasome Modulates Disease Progression in a Chronic-Plus-Binge Mouse Model of Alcoholic Liver Disease. Cells, 11.","DOI":"10.3390\/cells11020182"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/j.bbrc.2020.05.171","article-title":"NLRP6 exerts a protective role via NF-kB with involvement of CCL20 in a mouse model of alcoholic hepatitis","volume":"528","author":"Ji","year":"2020","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"751374","DOI":"10.1155\/2013\/751374","article-title":"Alcohol-induced liver injury is modulated by Nlrp3 and Nlrc4 inflammasomes in mice","volume":"2013","author":"DeSantis","year":"2013","journal-title":"Mediat. Inflamm."},{"key":"ref_87","first-page":"e20220001","article-title":"Cannabis legalization in the U.S. Where do we go from here?","volume":"44","author":"Martins","year":"2022","journal-title":"Trends Psychiatry Psychother."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"412","DOI":"10.5740\/jaoacint.18-0208","article-title":"A Brief Background on Cannabis: From Plant to Medical Indications","volume":"102","author":"Klumpers","year":"2019","journal-title":"J. AOAC Int."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Calapai, F., Cardia, L., Sorbara, E.E., Navarra, M., Gangemi, S., Calapai, G., and Mannucci, C. (2020). Cannabinoids, Blood-Brain Barrier, and Brain Disposition. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12030265"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1111\/adb.12714","article-title":"Cerebellar alterations in cannabis users: A systematic review","volume":"24","author":"Blithikioti","year":"2019","journal-title":"Addict. Biol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1146\/annurev-neuro-062111-150420","article-title":"Multiple functions of endocannabinoid signaling in the brain","volume":"35","author":"Katona","year":"2012","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1097\/ACO.0000000000000616","article-title":"An overview of the cannabinoid type 2 receptor system and its therapeutic potential","volume":"31","author":"Bie","year":"2018","journal-title":"Curr. Opin. Anaesthesiol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"2816","DOI":"10.1172\/JCI67569","article-title":"Microglial activation underlies cerebellar deficits produced by repeated cannabis exposure","volume":"123","author":"Cutando","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Suryavanshi, S.V., Zaiachuk, M., Pryimak, N., Kovalchuk, I., and Kovalchuk, O. (2022). Cannabinoids Alleviate the LPS-Induced Cytokine Storm via Attenuating NLRP3 Inflammasome Signaling and TYK2-Mediated STAT3 Signaling Pathways In Vitro. Cells, 11.","DOI":"10.20944\/preprints202204.0077.v1"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"613613","DOI":"10.3389\/fimmu.2020.613613","article-title":"Cannabinoids as Key Regulators of Inflammasome Signaling: A Current Perspective","volume":"11","author":"Suryavanshi","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1002\/glia.23738","article-title":"Cannabidiol prevents LPS-induced microglial inflammation by inhibiting ROS\/NF-kappaB-dependent signaling and glucose consumption","volume":"68","author":"Guimaraes","year":"2020","journal-title":"Glia"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1124\/jpet.119.260661","article-title":"Delta(9)-Tetrahydrocannabinol Suppresses Monocyte-Mediated Astrocyte Production of Monocyte Chemoattractant Protein 1 and Interleukin-6 in a Toll-Like Receptor 7-Stimulated Human Coculture","volume":"371","author":"Rizzo","year":"2019","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"2246","DOI":"10.1002\/ptr.7458","article-title":"Non-psychotropic Cannabis sativa L. phytocomplex modulates microglial inflammatory response through CB2 receptors-, endocannabinoids-, and NF-kappaB-mediated signaling","volume":"36","author":"Borgonetti","year":"2022","journal-title":"Phytother. Res."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1007\/s10571-011-9692-3","article-title":"The non-psychoactive plant cannabinoid, cannabidiol affects cholesterol metabolism-related genes in microglial cells","volume":"31","author":"Rimmerman","year":"2011","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1111\/cns.12349","article-title":"Activating cannabinoid receptor 2 alleviates pathogenesis of experimental autoimmune encephalomyelitis via activation of autophagy and inhibiting NLRP3 inflammasome","volume":"20","author":"Shao","year":"2014","journal-title":"CNS Neurosci. Ther."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1177\/00220345211024528","article-title":"CBD Promotes Oral Ulcer Healing via Inhibiting CMPK2-Mediated Inflammasome","volume":"101","author":"Qi","year":"2022","journal-title":"J. Dent. Res."},{"key":"ref_102","unstructured":"Hedegaard, H., Minino, A.M., and Warner, M. (2020). Drug Overdose Deaths in the United States, 1999\u20132019. NCHS Data Brief., 1\u20138."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.4049\/jimmunol.1400106","article-title":"Chronic morphine-induced microRNA-124 promotes microglial immunosuppression by modulating P65 and TRAF6","volume":"194","author":"Qiu","year":"2015","journal-title":"J. Immunol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1186\/s12974-022-02453-7","article-title":"Morphine-induced microglial immunosuppression via activation of insufficient mitophagy regulated by NLRX1","volume":"19","author":"Peng","year":"2022","journal-title":"J. Neuroinflamm."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Terminel, M.N., Bassil, C., Rau, J., Trevino, A., Ruiz, C., Alaniz, R., and Hook, M.A. (2022). Morphine-induced changes in the function of microglia and macrophages after acute spinal cord injury. BMC Neurosci., 23.","DOI":"10.1186\/s12868-022-00739-3"},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Yang, Y., Sun, Y., Hu, R., Yan, J., Wang, Z., Li, W., and Jiang, H. (2021). Morphine promotes microglial activation by upregulating the EGFR\/ERK signaling pathway. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0256870"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"6325","DOI":"10.1073\/pnas.1200130109","article-title":"Morphine activates neuroinflammation in a manner parallel to endotoxin","volume":"109","author":"Wang","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.3389\/fimmu.2020.01455","article-title":"Toll-like Receptor 4 (TLR4)\/Opioid Receptor Pathway Crosstalk and Impact on Opioid Analgesia, Immune Function, and Gastrointestinal Motility","volume":"11","author":"Zhang","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"6713","DOI":"10.1007\/s12035-018-0878-2","article-title":"Morphine-Mediated Brain Region-Specific Astrocytosis Involves the ER Stress-Autophagy Axis","volume":"55","author":"Sil","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.14336\/AD.2021.0406","article-title":"Astrocytes & Astrocyte derived Extracellular Vesicles in Morphine Induced Amyloidopathy: Implications for Cognitive Deficits in Opiate Abusers","volume":"12","author":"Sil","year":"2021","journal-title":"Aging Dis."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1186\/s12974-016-0520-z","article-title":"Procyanidins alleviates morphine tolerance by inhibiting activation of NLRP3 inflammasome in microglia","volume":"13","author":"Cai","year":"2016","journal-title":"J. Neuroinflamm."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"E3441","DOI":"10.1073\/pnas.1602070113","article-title":"Morphine paradoxically prolongs neuropathic pain in rats by amplifying spinal NLRP3 inflammasome activation","volume":"113","author":"Grace","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.bbi.2017.08.018","article-title":"Protraction of neuropathic pain by morphine is mediated by spinal damage associated molecular patterns (DAMPs) in male rats","volume":"72","author":"Grace","year":"2018","journal-title":"Brain Behav. Immun."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"571","DOI":"10.2147\/JIR.S266995","article-title":"Spinal TLR4\/P2X7 Receptor-Dependent NLRP3 Inflammasome Activation Contributes to the Development of Tolerance to Morphine-Induced Antinociception","volume":"13","author":"Wang","year":"2020","journal-title":"J. Inflamm. Res."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"105482","DOI":"10.1016\/j.phrs.2021.105482","article-title":"Microglial TLR4-induced TAK1 phosphorylation and NLRP3 activation mediates neuroinflammation and contributes to chronic morphine-induced antinociceptive tolerance","volume":"165","author":"Wang","year":"2021","journal-title":"Pharmacol. Res."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1007\/s10571-020-00957-5","article-title":"Morphine and Fentanyl Repeated Administration Induces Different Levels of NLRP3-Dependent Pyroptosis in the Dorsal Raphe Nucleus of Male Rats via Cell-Specific Activation of TLR4 and Opioid Receptors","volume":"42","author":"Rice","year":"2022","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"111442","DOI":"10.1016\/j.biopha.2021.111442","article-title":"Targeting the NLRP3 inflammasome as new therapeutic avenue for inflammatory bowel disease","volume":"138","author":"Chen","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"2520","DOI":"10.1007\/s12035-023-03229-7","article-title":"The Potential of NLRP3 Inflammasome as a Therapeutic Target in Neurological Diseases","volume":"60","author":"He","year":"2023","journal-title":"Mol. Neurobiol."},{"key":"ref_119","first-page":"11297298221124730","article-title":"Pentoxifylline decreases the activity of the nucleotide-binding oligomerization domain-like receptor protein 3 pathway: Potential role for preventing arteriovenous fistula stenosis","volume":"10","author":"Feng","year":"2022","journal-title":"J. Vasc. Access"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1159\/000452172","article-title":"Minocycline Suppresses NLRP3 Inflammasome Activation in Experimental Ischemic Stroke","volume":"23","author":"Lu","year":"2016","journal-title":"Neuroimmunomodulation"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"650283","DOI":"10.3389\/fphar.2021.650283","article-title":"Ibudilast Attenuates Folic Acid-Induced Acute Kidney Injury by Blocking Pyroptosis Through TLR4-Mediated NF-kappaB and MAPK Signaling Pathways","volume":"12","author":"Li","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_122","first-page":"1812","article-title":"Pioglitazone ameliorates retinal ischemia\/reperfusion injury via suppressing NLRP3 inflammasome activities","volume":"10","author":"Zhang","year":"2017","journal-title":"Int. J. Ophthalmol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"108654","DOI":"10.1016\/j.exer.2021.108654","article-title":"N-acetylcysteine alleviates ocular surface damage in STZ-induced diabetic mice by inhibiting the ROS\/NLRP3\/Caspase-1\/IL-1beta signaling pathway","volume":"209","author":"Liu","year":"2021","journal-title":"Exp. Eye Res."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1936","DOI":"10.7150\/ijms.44330","article-title":"Inhibiting Caspase-12 Mediated Inflammasome Activation protects against Oxygen-Glucose Deprivation Injury in Primary Astrocytes","volume":"17","author":"Liu","year":"2020","journal-title":"Int. J. Med. Sci."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"2422","DOI":"10.1016\/j.neuron.2022.05.009","article-title":"Neuronal NLRP3 is a parkin substrate that drives neurodegeneration in Parkinson\u2019s disease","volume":"110","author":"Panicker","year":"2022","journal-title":"Neuron"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/13\/6\/922\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:46:19Z","timestamp":1760125579000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/13\/6\/922"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,31]]},"references-count":125,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2023,6]]}},"alternative-id":["biom13060922"],"URL":"https:\/\/doi.org\/10.3390\/biom13060922","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,31]]}}}