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Targeting the Kynurenine Pathway to Improve Mood Disorders.

Ricardo Tadeu de Carvalho1,2, Izabela Guimarães Barbosa1,3, Fabrício A Moreira4

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Summary

The kynurenine pathway (KP) is implicated in major depressive disorder (MDD) and bipolar disorder (BD). Targeting the KP offers a promising therapeutic strategy for these debilitating mood disorders.

Keywords:
Kynurenine pathwaybipolar disordermajor depressive disordermood disorderstryptophan.

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Area of Science:

  • Neuroscience
  • Psychiatry
  • Pharmacology

Background:

  • Major depressive disorder (MDD) and bipolar disorder (BD) are leading causes of disability.
  • Current treatments targeting monoamines often result in treatment resistance.
  • The kynurenine pathway (KP) is increasingly recognized for its role in mood disorder pathophysiology.

Purpose of the Study:

  • To review the role of the kynurenine pathway (KP) in mood disorders.
  • To explore KP-modulating therapies and potential therapeutic targets.
  • To identify knowledge gaps in KP research for mood disorders.

Main Methods:

  • Narrative review of literature from PubMed and Embase databases.
  • Discussion of KP modulation by existing therapies (antidepressants, neuromodulation, NMDAR antagonists).
  • Examination of preclinical and clinical evidence for KP-targeted therapeutics.

Main Results:

  • MDD and BD are linked to a shift towards neuroprotective KP metabolites.
  • KP alterations correlate with inflammation and brain structural changes.
  • Several KP targets (IDO, TDO, KMO inhibitors, KYNA mimetics) show therapeutic potential.

Conclusions:

  • The kynurenine pathway (KP) presents a novel therapeutic avenue for mood disorders.
  • Further research is needed on less-studied KP molecules and mania.
  • More preclinical and clinical trials are required for KP-targeted drugs.