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Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Psychiatr. Dec 19, 2021; 11(12): 1191-1205
Published online Dec 19, 2021. doi: 10.5498/wjp.v11.i12.1191
Nuclear receptors modulate inflammasomes in the pathophysiology and treatment of major depressive disorder
Han Wang, Wei-Jing Kan, Yuan Feng, Lei Feng, Yang Yang, Pei Chen, Jing-Jie Xu, Tian-Mei Si, Ling Zhang, Gang Wang, Jing Du
Han Wang, Wei-Jing Kan, Yuan Feng, Lei Feng, Yang Yang, Pei Chen, Jing-Jie Xu, Ling Zhang, Gang Wang, Jing Du, The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Beijing 100088, Beijing Province, China
Tian-Mei Si, Department of Clinical Psychopharmacology, Peking University Institute of Mental Health, Beijing 100191, Beijing Province, China
Jing Du, State Key Laboratory for Conservation and Utilization of Bio-resources in Yunnan, Yunnan University, Kunming 650091, Yunnan Province, China
Author contributions: Wang H wrote the first draft of the manuscript; Kan WJ, Feng Y, Feng L, Yang Y, Chen P, and Xu JJ managed the systematic literature search; Du J supervised the study; Si TM, Zhang L, and Wang G critically revised the manuscript; and all authors approved the final version of the manuscript.
Supported by the National Natural Science Foundation of China, No. 31650005.
Conflict-of-interest statement: The authors declare no conflict of interest for this manuscript.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Jing Du, PhD, Professor, The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, No. 5 Ankanghutong, Western City District, Beijing 100088, Beijing Province, China. 2648215772@qq.com
Received: March 1, 2021
Peer-review started: March 1, 2021
First decision: July 15, 2021
Revised: July 29, 2021
Accepted: November 2, 2021
Article in press: November 2, 2021
Published online: December 19, 2021
Processing time: 289 Days and 5.3 Hours
Abstract

Major depressive disorder (MDD) is highly prevalent and is a significant cause of mortality and morbidity worldwide. Currently, conventional pharmacological treatments for MDD produce temporary remission in < 50% of patients; therefore, there is an urgent need for a wider spectrum of novel antidepressants to target newly discovered underlying disease mechanisms. Accumulated evidence has shown that immune inflammation, particularly inflammasome activity, plays an important role in the pathophysiology of MDD. In this review, we summarize the evidence on nuclear receptors (NRs), such as glucocorticoid receptor, mineralocorticoid receptor, estrogen receptor, aryl hydrocarbon receptor, and peroxisome proliferator-activated receptor, in modulating the inflammasome activity and depression-associated behaviors. This review provides evidence from an endocrine perspective to understand the role of activated NRs in the pathophysiology of MDD, and to provide insight for the discovery of antidepressants with novel mechanisms for this devastating disorder.

Keywords: Major depressive disorder; Immune inflammation; Inflammasome; Nuclear receptors

Core Tip: We summarize the evidence on nuclear receptors (NRs), such as glucocorticoid receptor, mineralocorticoid receptor, estrogen receptor, aryl hydrocarbon receptor, and peroxisome proliferator-activated receptor, in modulating inflammasome activity and depression-associated behaviors. This review provides evidence from an endocrine perspective to understand the role of activated NRs in the pathophysiology and treatment of major depressive disorder. Hopefully, the modulation of NRs with hormones and metabolites may become one of the key endocrinologic mechanisms for the development of novel therapeutics to increase the likelihood of therapeutic efficacy.