The interaction between autophagy and neuroinflammation in major depressive disorder: From pathophysiology to therapeutic implications

The past decade has revealed neuroinflammation as an important mechanism of major depressive disorder (MDD). Nod-like receptors family pyrin domain containing 3 (NLRP3) inflammasome is the key regulator interleukin-1 beta (IL-1 beta) maturation, whose activation has been reported in MDD patients and various animal models. Function as a dominant driver of neuroinflammation, NLRP3 bridges the gap between immune activation with stress exposure, and further leads to subsequent occurrence of neuropsychiatric disorders such as MDD. Of note, autophagy is a tightly regulated cellular degradation pathway that removes damaged organelles and intracellular pathogens, and maintains cellular homeostasis from varying insults. Serving as a critical cellular monitoring system, normal functioned autophagy signaling prevents excessive NLRP3 inflammasome activation and subsequent release of IL-1 family cytokines. This review will describe the current understanding of how autophagy regulates NLRP3 inflammasome activity and discuss the implications of this regulation on the pathogenesis of MDD. The extensive crosstalk between autophagy pathway and NLRP3 inflammasome is further discussed, as it is critical for developing new therapeutic strategies for MDD aimed at modulating the neuro-inflammatory responses.

Automated summary

Neuroinflammation has been identified as an important mechanism of major depressive disorder, with the NLRP3 inflammasome playing a critical role in its pathogenesis. The autophagy signaling pathway is essential for regulating NLRP3 inflammasome activity, preventing excessive activation and release of inflammatory cytokines.