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Emerging cell death in depression: Mechanisms and therapeutic implications

Chuang Jin1, Yuhui Li2

  • 1Department of Nursing, Shengjing Hospital of China Medical University, No. 36, Sanhao Street, Heping District, Shenyang, Liaoning Province 110004, China.

Progress in Neuro-Psychopharmacology & Biological Psychiatry
|June 24, 2026
PubMed

Insights

Major depressive disorder (MDD) research is exploring novel cell death pathways like ferroptosis and pyroptosis. Targeting these regulated cell death (RCD) mechanisms with natural products may offer new therapeutic strategies for MDD.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Pharmacology

Background:

  • Major depressive disorder (MDD) is a prevalent psychiatric condition with complex, incompletely understood pathological mechanisms.
  • Current treatments for MDD yield unsatisfactory outcomes for many patients, highlighting the need for novel therapeutic targets.
  • Emerging regulated cell death (RCD) pathways, including ferroptosis and pyroptosis, are increasingly implicated in neurological and psychiatric disorders.

Purpose of the Study:

  • To review the molecular mechanisms of emerging RCD pathways (ferroptosis, pyroptosis, cuproptosis).
  • To explore the roles of ferroptosis and pyroptosis in the pathogenesis and treatment modulation of MDD.
  • To examine natural products and traditional Chinese medicine as potential therapeutic agents targeting these RCD pathways in MDD.

Main Methods:

  • Literature review focusing on preclinical studies.
  • Analysis of molecular mechanisms underlying ferroptosis, pyroptosis, and cuproptosis.
  • Synthesis of evidence linking RCD pathways to MDD pathogenesis and treatment.

Main Results:

  • Ferroptosis and pyroptosis are closely involved in MDD pathogenesis.
  • These RCD pathways are potential targets for therapeutic modulation in MDD.
  • Natural products and traditional Chinese medicine show promise in targeting RCD pathways for MDD treatment, primarily based on preclinical data.

Conclusions:

  • Emerging RCD pathways offer novel insights into MDD pathophysiology.
  • Targeting ferroptosis and pyroptosis presents a promising avenue for developing new MDD therapies.
  • Further research, particularly clinical studies, is needed to validate natural products and traditional Chinese medicine for MDD treatment via RCD modulation.
Keywords:
FerroptosisMajor depressive disorderNeuroinflammationPharmacological mechanismsPyroptosisRegulated cell death

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