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Journal Article
Review
Targeting inflammasome complexes as a novel therapeutic strategy for mood disorders.
Expert Opinion on Therapeutic Targets 2024 June 13
INTRODUCTION: Inflammasome complexes, especially the NLRP3, have gained great attention as a potential therapeutic target in mood disorders. NLRP3 triggers a caspase 1-dependent release of the inflammatory cytokines IL-1β and IL-18, and seems to interact with purinergic and kynurenine pathways, all of which are implicated in mood disorders development and progression.
AREAS COVERED: Emerging evidence supports NLRP3 inflammasome as promising pharmacological targets for mood disorders. We discussed the available evidence from animal models and human studies and provided a reflection on drawbacks and perspectives for this novel target.
EXPERT OPINION: Several studies have supported the involvement of NLRP3 inflammasome in MDD. However, most evidence comes from animal models. The role of NLRP3 inflammasome in BD as well as its anti-manic properties are not very clear and require further exploration. There is evidence of anti-manic effects of P2×R7antagonists associated with reduction in the brain levels of IL-1β and TNF-α in a murine model of mania. The involvement of other NLRP3 inflammasome expressing cells besides microglia, like astrocytes, and of other inflammasome complexes in mood disorders also deserves further investigation. Preclinical and clinical characterization of NLRP3 and other inflammasomes in mood disorders is needed before considering translational approaches, including clinical trials.
AREAS COVERED: Emerging evidence supports NLRP3 inflammasome as promising pharmacological targets for mood disorders. We discussed the available evidence from animal models and human studies and provided a reflection on drawbacks and perspectives for this novel target.
EXPERT OPINION: Several studies have supported the involvement of NLRP3 inflammasome in MDD. However, most evidence comes from animal models. The role of NLRP3 inflammasome in BD as well as its anti-manic properties are not very clear and require further exploration. There is evidence of anti-manic effects of P2×R7antagonists associated with reduction in the brain levels of IL-1β and TNF-α in a murine model of mania. The involvement of other NLRP3 inflammasome expressing cells besides microglia, like astrocytes, and of other inflammasome complexes in mood disorders also deserves further investigation. Preclinical and clinical characterization of NLRP3 and other inflammasomes in mood disorders is needed before considering translational approaches, including clinical trials.
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