Redefining Roles: A Paradigm Shift in Tryptophan–Kynurenine Metabolism for Innovative Clinical Applications

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(23), P. 12767 - 12767

Published: Nov. 27, 2024

The tryptophan-kynurenine (KYN) pathway has long been recognized for its essential role in generating metabolites that influence various physiological processes. Traditionally, these have categorized into distinct, often opposing groups, such as pro-oxidant versus antioxidant, excitotoxic/neurotoxic neuroprotective. This dichotomous framework shaped much of the research on conditions like neurodegenerative and neuropsychiatric disorders, well cancer, where metabolic imbalances are a key feature. effects significantly influenced by factors, including concentration particular cellular milieu which they generated. A molecule acts neuroprotective at low concentrations may exhibit neurotoxic elevated levels. oxidative equilibrium surrounding environment can alter function KYN from an antioxidant to pro-oxidant. narrative review offers comprehensive examination analysis contemporary understanding metabolites, emphasizing their multifaceted biological functions relevance numerous pathological underscores pressing necessity paradigm shift comprehension metabolism. Understanding context-dependent roles is vital novel therapies Alzheimer's disease, multiple sclerosis, cancer. Comprehensive modulation, balancing inflammatory signals enzyme regulation, promising avenues targeted, effective treatments.

Language: Английский

---

Urinary metabolic alterations associated with occupational exposure to metals and polycyclic aromatic hydrocarbons based on non-target metabolomics

Journal of Hazardous Materials, Journal Year: 2025, Volume and Issue: 487, P. 137158 - 137158

Published: Jan. 8, 2025

Language: Английский

---

Unveiling new perspectives about the onset of neurological and cognitive deficits in cerebral malaria: exploring cellular and neurochemical mechanisms

Frontiers in Cellular and Infection Microbiology, Journal Year: 2025, Volume and Issue: 15

Published: Feb. 6, 2025

Cerebral malaria is the most severe and lethal complication caused by Plasmodium falciparum infection, leading to critical neurological impairments long-term cognitive, behavioral, sequelae in survivors, particularly affecting children under age of five. Various hypotheses have been proposed explain syndrome associated cerebral condition, including vascular occlusion sequestration, cytokine storm or inflammatory response, a combination these mechanisms despite extensive research growing range scientific information, precise pathophysiological mechanism remains poorly understood. In this sense, review aims explore impairment elucidate novel severity disease. Recent evidence implicates glutamate glutamatergic pathways onset malaria, alongside metabolic activity other molecules such as dopamine kynurenic acid. These neurotransmitters may play crucial role pathogenesis potentially interacting with molecular players. By enhancing our understanding pathophysiology article seeks new regarding involvement their interactions targets, thereby contributing overall pathology malaria.

Language: Английский

---

The role of the gut microbiome in Alzheimer's disease pathophysiology

Current Opinion in Neurology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 7, 2025

Purpose of review The present aims to provide an overview the existing understanding role gut microbiome in Alzheimer's disease pathophysiology. Recent findings research has highlighted significant pathogenesis via gut-brain axis. However, precise mechanisms by which and its microbial metabolites influence brain function are not clearly understood. Various factors, such as diet, drugs, lifestyle, stress, infections can provoke imbalance homeostasis, known dysbiosis. This dysbiosis impacts intestinal blood-brain barrier permeability, elevating pro-inflammatory cytokines contributing neurodegeneration. Moreover, generates neurotransmitters, amyloids, neurotoxins, metabolites, may play a systemic inflammation disruption physiological barriers. Summary In past decade, advancements analysis technologies bioinformatics have significantly enhanced our disease. plays pivotal regulatory progression disease, closely interacts with pathogenesis, encompassing inflammation, amyloidosis, neurodegeneration, tauopathy, co-pathologies.

Language: Английский

---

Metabolic Reprogramming in Response to Freund’s Adjuvants: Insights from Serum Metabolomics

Microorganisms, Journal Year: 2025, Volume and Issue: 13(3), P. 492 - 492

Published: Feb. 22, 2025

Freund’s adjuvants have been used in vaccine and autoimmune settings, their effects can be overlapping or unique to each. While both incomplete (IFA) complete (CFA) influence antibody T cell responses, the robust helper 1 cytokines induced by mycobacterial components make CFA powerful immunostimulating adjuvant. In these studies, adjuvant are investigated a select population of cells, changes, if any, with metabolic alterations systemic compartment unclear. We whether IFA influenced shifts mice immunized saline, IFA, using Mycobacterium tuberculosis var. bovis Bacillus Calmette–Guérin (BCG) as positive control. After seven days immunization, we analyzed serum metabolite profiles liquid chromatography coupled high-resolution mass spectrometry multivariate statistical analysis identify features between groups. The data revealed that, scores space, BCG groups were more closely aligned compared saline group, while group displayed an intermediate profile. Furthermore, comparisons showed significant perturbations lipid amino acid metabolism, particularly involving glycerophospholipids, cysteine, aromatic acids. contrast, indicated pronounced disruption central energy metabolism pathways, such citric cycle pyruvate metabolism. Together, suggest that response might play role modulating immune responses.

Language: Английский

---