title: The Potential Role of the NLRP3 Inflammasome as a Link between Mitochondrial Complex I Dysfunction and Inflammation in Bipolar Disorder.
abstract: Mitochondrial dysfunction and activation of the inflammatory system are two of the most consistently reported findings in bipolar disorder (BD). More specifically, altered levels of inflammatory cytokines and decreased levels of mitochondrial complex I subunits have been found in the brain and periphery of patients with BD, which could lead to increased production of mitochondrial reactive oxygen species (ROS). Recent studies have shown that mitochondrial production of ROS and inflammation may be closely linked through a redox sensor known as nod-like receptor pyrin domain-containing 3 (NLRP3). Upon sensing mitochondrial release of ROS, NLRP3 assembles the NLRP3 inflammasome, which releases caspase 1 to begin the inflammatory cascade. In this review, we discuss the potential role of the NLRP3 inflammasome as a link between complex I dysfunction and inflammation in BD and its therapeutic implications.
authors.affiliation: Department of Pharmacology and Toxicology, University of Toronto, 1 King's College Circle, Toronto, ON, Canada M5S 1A8.
authors.forename: Helena Kyunghee
authors.initials: HK
authors.lastname: Kim
authors.affiliation: Department of Pharmacology and Toxicology, University of Toronto, 1 King's College Circle, Toronto, ON, Canada M5S 1A8.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Pharmacology and Toxicology, University of Toronto, 1 King's College Circle, Toronto, ON, Canada M5S 1A8 ; Department of Psychiatry, University of Toronto, 1 King's College Circle, Toronto, ON, Canada M5S 1A8 ; Centre of Addiction and Mental Health, 250 College Street, Toronto, ON, Canada M5T 1R8.
authors.forename: Ana Cristina
authors.initials: AC
authors.lastname: Andreazza
mesh_terms: D000818:Animals; D001714:Bipolar Disorder / Q000209:etiology / Q000276:immunology / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D042967:Electron Transport Complex I / Q000378:metabolism*; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism; D007249:Inflammation / Q000150:complications / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism; D028361:Mitochondrial Diseases / Q000150:complications / Q000378:metabolism*; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D018384:Oxidative Stress; D017382:Reactive Oxygen Species
chemical_list: D002352:Carrier Proteins; D058847:Inflammasomes; D018836:Inflammation Mediators; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D017382:Reactive Oxygen Species; D042967:Electron Transport Complex I