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Related Experiment Video

Updated: Jun 10, 2026

Network Pharmacology and Validation of the Antidepressant Mechanisms of Qiangzhifang in a Chronic Restraint Stress-induced Depression Rat Model
08:15

Network Pharmacology and Validation of the Antidepressant Mechanisms of Qiangzhifang in a Chronic Restraint Stress-induced Depression Rat Model

Published on: June 6, 2025

Targeting Neuroinflammation in Depression: The Integrative Role of Sigma-1 Receptor Modulation.

Jing-Ya Wang1, De-Yi Yang1,2, Yun-Feng Li1

  • 1Academy of Military Medical Sciences, Beijing, China.

Journal of Neurochemistry
|June 9, 2026
PubMed
Summary

Depression treatment may improve by targeting neuroinflammation via Sigma-1 receptor (Sig-1R) agonists. These compounds address cellular stress and immune pathways, offering a novel therapeutic approach beyond traditional antidepressants.

Keywords:
antidepressantdepressionneuroinflammationsigma‐1 receptor

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Last Updated: Jun 10, 2026

Network Pharmacology and Validation of the Antidepressant Mechanisms of Qiangzhifang in a Chronic Restraint Stress-induced Depression Rat Model
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Modeling Neural Immune Signaling of Episodic and Chronic Migraine Using Spreading Depression In Vitro
16:13

Modeling Neural Immune Signaling of Episodic and Chronic Migraine Using Spreading Depression In Vitro

Published on: June 13, 2011

Area of Science:

  • Neuroscience
  • Immunology
  • Pharmacology

Background:

  • Depression is a leading cause of disability with limited conventional treatment efficacy.
  • Neuroinflammation, glial dysfunction, and cellular stress are implicated in depression pathogenesis.
  • Conventional antidepressants have delayed onset, variable efficacy, and side effects.

Purpose of the Study:

  • To review the role of the Sigma-1 receptor (Sig-1R) as a therapeutic target for depression.
  • To synthesize evidence on Sig-1R activation's anti-neuroinflammatory and cellular protective effects.
  • To evaluate Sig-1R agonists and clinical data for depression treatment.

Main Methods:

  • Systematic synthesis of preclinical evidence on Sig-1R activation.
  • Review of Sigma-1 receptor agonist advancements.
  • Evaluation of clinical trial data, including AXS-05.
  • Analysis of genetic and pharmacological loss-of-function studies.

Main Results:

  • Sig-1R activation demonstrates broad anti-neuroinflammatory effects, including microglial homeostasis and reduced astrogliosis.
  • It alleviates endoplasmic reticulum stress, enhances autophagy/mitophagy, and supports mitochondrial function.
  • Sig-1R agonists show potential in mood regulation and stress resilience, disrupting the inflammation-stress cycle.

Conclusions:

  • The Sigma-1 receptor is a key regulator of cellular homeostasis and adaptation in depression.
  • Sig-1R agonists offer a mechanistically targeted approach for depression, addressing inflammation and proteostatic dysfunction.
  • This strategy holds potential for improved treatment efficacy beyond monoaminergic modulation.