Neuroprotective Effect of Fluoxetine Via Targeting Nlrp3 Inflammasome-Autophagy Crosstalk Publisher



Nazari S ; Pourmand SM ; Motevaseli E ; Hassanzadeh G
Source: Journal of Contemporary Medical Sciences Published:2025

Abstract

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. © 2025, Nab'a Al-Hayat Foundation for Medical Sciences and Health Care. All rights reserved.