Evidence map›Paper›PMID 41516008›Full record

ReviewInternational journal of molecular sciences2025

Kynurenine Pathway Metabolites as Mediators of Exercise-Induced Mood Enhancement, Fatigue Resistance, and Neuroprotection.

Amelia Tero-Vescan, Ruxandra Ștefănescu, Amalia Pușcaș, Mădălina Buț, Bianca-Eugenia Ősz, Mark Slevin

Abstract readReview
In one paragraph

Review in International journal of molecular sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Review
  4. Review
  5. Article
  6. Review
  7. Review
  8. Review
  9. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Amelia Tero-VescanBiochemistry Department, Faculty of Medicine in English, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mureș, 540142 Târgu Mureș, Romania.ORCID 0009-0000-9704-869X
Ruxandra ȘtefănescuPharmacognosy and Phytotherapy Department, Faculty of Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mureș, 540142 Târgu Mureș, Romania.ORCID 0000-0002-3346-3867
Amalia PușcașBiochemistry Department, Faculty of Medicine in English, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mureș, 540142 Târgu Mureș, Romania.
Mădălina BuțBiochemistry Department, Faculty of Medicine in English, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mureș, 540142 Târgu Mureș, Romania.
Bianca-Eugenia ŐszPharmacology and Clinical Pharmacy Department, Faculty of Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mureș, 540142 Târgu Mureș, Romania.
Mark SlevinCenter for Advanced Medical and Pharmaceutical Research, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mureș, 540142 Târgu Mureș, Romania.ORCID 0000-0003-3767-4861

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Major depressive disorder is increasingly recognized as a metabolic-immune disorder in which chronic inflammation diverts tryptophan (Trp) metabolism toward the kynurenine pathway (KP), reducing serotonin synthesis and producing neurotoxic metabolites such as quinolinic acid (QA). Elevated kynurenine (KYN)/Trp ratios and an altered QA/kynurenic acid (KYNA) balance have been consistently reported in depressed individuals, implicating the KP as a key therapeutic target. Exercise provides a unique, translationally relevant intervention: unlike pharmacological agents acting directly on neurotransmission, contracting skeletal muscle acts as a "kynurenine sink" by inducing kynurenine aminotransferases that convert circulating KYN into neuroprotective KYNA, thereby reducing brain KYN uptake and mitigating excitotoxicity. Clinical studies and meta-analyses confirm that aerobic, resistance, and high-intensity training produce antidepressant effects comparable to pharmacotherapy, while also improving cognition, fatigue tolerance, and cardiometabolic function. Beyond KP remodeling, exercise-induced myokines (irisin, IL-6, BDNF, apelin, FGF21) and adipokines (adiponectin, leptin modulators) coordinate systemic anti-inflammatory and neurotrophic adaptations that enhance resilience and brain plasticity. Furthermore, pharmacological "exercise mimetics" and metabolic modulators, such as PPAR agonists, AMPK activators, NAD

Indexed as

ExerciseKynurenineNeuroprotectionAnimalsHumansMetabolic Networks and PathwaysMyokinesSignal TransductionTryptophanKynurenineMyokinesTryptophanadiponectinexerciseexercise mimeticsHIITirisinkynurenic acidkynurenine pathwayleptinmajor depressive disorderquinolinic acid

Identifiers

PMID41516008
PMCPMC12785747

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.