Neuroprotective Effect of Fluoxetine via Targeting NLRP3 Inflammasome-Autophagy Crosstalk
DOI:
https://doi.org/10.22317/jcms.v11i6.2073Keywords:
Fluoxetine, NLRP3 Inflammasome, Inflammasomes, Autophagy, Neuroinflammation, Central Nervous SystemAbstract
Fluoxetine, a selective serotonin reuptake inhibitor (SSRI) approved for major depressive disorder, exerts neuroprotective effects by modulating the NLRP3 inflammasome-autophagy crosstalk central to neuroinflammation in CNS disorders. This review synthesizes evidence demonstrating fluoxetine's dual mechanisms: direct inhibition of NLRP3 assembly and activation (reducing IL-1β/IL-18 release via NACHT domain binding and ROS mitigation through Nrf2/HO-1 pathways) alongside enhancement of autophagic flux (elevating LC3-II, Beclin-1, ATG5, and p62/SQSTM1), which promotes autophagic degradation of inflammasome components. This review highlights the need for deeper mechanistic insights into fluoxetine's regulation of autophagy-NLRP3 crosstalk, particularly through key regulatory proteins involved in this crosstalk. Enhanced understanding will unlock fluoxetine's full therapeutic potential for CNS disorder therapy.
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