Fleshner Monika, Frank Matthew, Maier Steven F
Department of Integrative Physiology, University of Colorado at Boulder, Boulder, CO, USA.
Center for Neuroscience, University of Colorado at Boulder, Boulder, CO, USA.
Neuropsychopharmacology. 2017 Jan;42(1):36-45. doi: 10.1038/npp.2016.125. Epub 2016 Jul 14.
Major depressive disorder (MDD) and other mood disorders remain difficult to effectively treat, and innovative interventions and therapeutic targets are needed. Psychological stressors and inappropriate inflammation increase the risk and severity of mood disorders; however, only recently have the importance of sterile inflammatory processes in this effect been revealed. This review will introduce the reader to pathogen vs sterile inflammation, inflammatory receptor-ligand interactions, microbial-associated molecular patterns (MAMPs), pathogen-associated molecular patterns (PAMPs), danger-associated molecular patterns (DAMPs), and the more recent discovery of the role of the inflammasome in peripheral and central nervous system cytokine/chemokine inflammatory responses. The review will focus on current preclinical and clinical evidence that sterile inflammation and inflammasome-dependent signaling may contribute to mood disorders. By understanding these inflammatory signaling processes, new approaches for quieting chronic or inappropriate inflammatory states may be revealed and this could serve as novel pharmacological targets for the treatment of mood disorders.
重度抑郁症（MDD）和其他情绪障碍仍然难以得到有效治疗，因此需要创新的干预措施和治疗靶点。心理压力源和不适当的炎症会增加情绪障碍的风险和严重程度；然而，直到最近，无菌性炎症过程在这种影响中的重要性才被揭示出来。这篇综述将向读者介绍病原体与无菌性炎症、炎症受体-配体相互作用、微生物相关分子模式（MAMPs）、病原体相关分子模式（PAMPs）、危险相关分子模式（DAMPs），以及最近关于炎性小体在周围和中枢神经系统细胞因子/趋化因子炎症反应中的作用的发现。这篇综述将聚焦于当前的临床前和临床证据，即无菌性炎症和炎性小体依赖性信号传导可能导致情绪障碍。通过了解这些炎症信号传导过程，或许可以揭示出平息慢性或不适当炎症状态的新方法，这可能成为治疗情绪障碍的新型药理学靶点。
