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June 11, 2026Journal of Neurochemistry

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

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Authors

YWYì WángDYDe‐Yi YangYLYunfeng Li

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Overview

Review examines Sigma-1 receptor modulation to alleviate neuroinflammation in depression, suggesting promising therapeutic implications.

Key Points

  • This review aims to explore the role of Sigma-1 receptor modulation in addressing neuroinflammation as a mechanism in depression.
  • Systematic synthesis of preclinical evidence on Sigma-1 receptor activation effects.
  • Evaluation of representative Sigma-1 receptor agonists and clinical trial data, including AXS-05.
  • Discussion of genetic and pharmacological loss-of-function studies to investigate Sigma-1 receptor's role.
  • Pharmacological activation of Sigma-1 receptor promotes anti-inflammatory microglial homeostasis and reduces reactive astrogliosis.
  • Sig-1R activation suppresses pro-inflammatory signals like NF-κB and NLRP3, mitigating cellular stress and synaptic impairment.
  • Loss-of-function studies indicate Sigma-1 receptor is essential for mood regulation and stress resilience.

Cite This Study

Wáng et al. (2026) studied this question.

synapsesocial.com/papers/6a2a523480c8f91e7f39e41ehttps://doi.org/10.1111/jnc.70490
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Advancing depression treatment: the role of sigma receptor ligands2025
  2. 2Advancing depression treatment: the role of sigma receptor ligands2025
  3. 3Targeting endoplasmic reticulum stress and protein misfolding in schizophrenia: the emerging promise of sigma-1 receptor agonists2025
  4. 4Activation of sigma non‐opioid intracellular receptor 1 (S1R) receptor inhibits plexin domain containing 2 (Plxdc2) driven microglial inflammation to ameliorate depressive‐like behaviours in mice2026
  5. 5Sigma-1R–CD36 axis in myeloid cells contributes to the alleviation of depression-like behaviors2026