title: NLRP3 inflammasome-driven pathways in depression: Clinical and preclinical findings.
abstract: Over the past three decades, an intricate interaction between immune activation, release of pro-inflammatory cytokines and changes in brain circuits related to mood and behavior has been described. Despite extensive efforts, questions regarding when inflammation becomes detrimental or how we can target the immune system to develop new therapeutic strategies for the treatment of psychiatric disorders remain unresolved. In this context, novel aspects of the neuroinflammatory process activated in response to stressful challenges have recently been documented in major depressive disorder (MDD). The Nod-like receptor pyrin containing 3 inflammasome (NLRP3) is an intracellular multiprotein complex responsible for a number of innate immune processes associated with infection, inflammation and autoimmunity. Recent data have demonstrated that NLRP3 activation appears to bridge the gap between immune activation and metabolic danger signals or stress exposure, which are key factors in the pathogenesis of psychiatric disorders. In this review, we discuss both preclinical and clinical evidence that links the assembly of the NLRP3 complex and the subsequent proteolysis and release of the pro-inflammatory cytokines interleukin-1β (IL-1β) and interleukin-18 (IL-18) in chronic stress models and patients with MDD. Importantly, we also focus on the therapeutic potential of targeting the NLRP3 inflammasome complex to improve stress resilience and depressive symptoms.
authors.affiliation: Department of Biochemistry, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil.
authors.forename: Fernanda N
authors.initials: FN
authors.lastname: Kaufmann
authors.affiliation: Department of Biochemistry, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil.
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Costa
authors.affiliation: Department of Life and Health Sciences, Catholic University of Pelotas, Rio Grande do Sul, Brazil.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Ghisleni
authors.affiliation: Postgraduate Program in Health Sciences, University of Southern Santa Catarina, Santa Catarina, Brazil.
authors.forename: Alexandre P
authors.initials: AP
authors.lastname: Diaz
authors.affiliation: Department of Biochemistry, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil.
authors.forename: Ana Lúcia S
authors.initials: ALS
authors.lastname: Rodrigues
authors.affiliation: Neuroinflammation and Gene Therapy Lab., Institut Pasteur de Montevideo, Uruguay; Dept. Histology and Embryology, Faculty of Medicine, UDELAR, Uruguay.
authors.forename: Hugo
authors.initials: H
authors.lastname: Peluffo
authors.affiliation: Department of Biochemistry, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil. Electronic address: manuella.kaster@ufsc.br.
authors.forename: Manuella P
authors.initials: MP
authors.lastname: Kaster
mesh_terms: D000818:Animals; D003865:Major Depressive Disorder / Q000150:complications / Q000276:immunology / Q000378:metabolism*; D004660:Encephalitis / Q000276:immunology / Q000378:metabolism*; D000069196:Gastrointestinal Microbiome; D006801:Humans; D058847:Inflammasomes / Q000276:immunology / Q000378:metabolism*; D017628:Microglia / Q000502:physiology; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000276:immunology / Q000378:metabolism*; D051192:Receptors, Pattern Recognition / Q000378:metabolism; D015398:Signal Transduction; D013315:Stress, Psychological / Q000150:complications* / Q000276:immunology / Q000378:metabolism
chemical_list: D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D051192:Receptors, Pattern Recognition
keywords: Cytokines; Depression; Inflammation; NLRP3; Stress