Molecular mechanisms and therapeutic significance of Tryptophan Metabolism and signaling in cancer

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: Oct. 30, 2024

Language: Английский

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The tryptophan metabolic pathway of the microbiome and host cells in health and disease

International Immunology, Journal Year: 2024, Volume and Issue: unknown

Published: June 13, 2024

Abstract The intricate and dynamic tryptophan (Trp) metabolic pathway in both the microbiome host cells highlights its profound implications for health disease. This involves complex interactions between cellular bacteria processes, producing bioactive compounds such as 5-hydroxytryptamine (5-HT) kynurenine derivatives. Immune responses to Trp metabolites through specific receptors have been explored, highlighting role of aryl hydrocarbon receptor inflammation modulation. Dysregulation this is implicated various diseases, Alzheimer’s Parkinson’s mood disorders, neuronal autoimmune diseases multiple sclerosis (MS), cancer. In article, we describe impact 5-HT, Trp, indole, on Furthermore, review microbiome-derived that affect immune contribute maintaining homeostasis, especially an experimental encephalitis model MS.

Language: Английский

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Targeting Cytokine-Mediated Inflammation in Brain Disorders: Developing New Treatment Strategies

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(1), P. 104 - 104

Published: Jan. 15, 2025

Cytokine-mediated inflammation is increasingly recognized for playing a vital role in the pathophysiology of wide range brain disorders, including neurodegenerative, psychiatric, and neurodevelopmental problems. Pro-inflammatory cytokines such as interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) cause neuroinflammation, alter function, accelerate disease development. Despite progress understanding these pathways, effective medicines targeting are still limited. Traditional anti-inflammatory immunomodulatory drugs peripheral inflammatory illnesses. Still, they face substantial hurdles when applied to central nervous system (CNS), blood-brain barrier (BBB) unwanted systemic effects. This review highlights developing treatment techniques modifying cytokine-driven focusing on advances that selectively target critical involved pathology. Novel approaches, cytokine-specific inhibitors, antibody-based therapeutics, gene- RNA-based interventions, sophisticated drug delivery systems like nanoparticles, show promise with respect lowering neuroinflammation greater specificity safety. Furthermore, developments biomarker discoveries neuroimaging improving our ability monitor responses, allowing more accurate personalized regimens. Preclinical clinical trial data demonstrate therapeutic potential tailored techniques. However, significant challenges remain, across BBB reducing off-target As research advances, creation personalized, cytokine-centered therapeutics has therapy landscape illnesses, giving patients hope better results higher quality life.

Language: Английский

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Lewy body diseases and the gut

Molecular Neurodegeneration, Journal Year: 2025, Volume and Issue: 20(1)

Published: Jan. 30, 2025

Abstract Gastrointestinal (GI) involvement in Lewy body diseases (LBDs) has been observed since the initial descriptions of patients by James Parkinson. Recent experimental and human observational studies raise possibility that pathogenic alpha-synuclein (⍺-syn) might develop GI tract subsequently spread to susceptible brain regions. The cellular mechanistic origins ⍺-syn propagation disease are under intense investigation. Experimental LBD models have implicated important contributions from intrinsic gut microbiome, intestinal immune system, environmental toxicants, acting as triggers modifiers pathologies. Here, we review primary clinical observations link dysfunctions LBDs. We first provide an overview anatomy repertoire relevant for disease, with a focus on luminal-sensing cells epithelium including enteroendocrine express make direct contact nerves. describe interactions within resident microbes exogenous how these may directly contribute pathology along related metabolic immunological responses. Finally, critical knowledge gaps field highlighted, focusing pivotal questions remain some 200 years after dysfunction predict better understanding pathophysiologies influence risk progression will accelerate discoveries lead deeper overall potential therapeutic strategies targeting gut-brain axis delay, arrest, or prevent progression.

Language: Английский

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Modulation of the Neuro–Cancer Connection by Metabolites of Gut Microbiota

Biomolecules, Journal Year: 2025, Volume and Issue: 15(2), P. 270 - 270

Published: Feb. 12, 2025

The gut-brain-cancer axis represents a novel and intricate connection between the gut microbiota, neurobiology, cancer progression. Recent advances have accentuated significant role of microbiota metabolites in modulating systemic processes that influence both brain health tumorigenesis. This paper explores emerging concept metabolite-mediated modulation within connection, focusing on key such as short-chain fatty acids (SCFAs), tryptophan derivatives, secondary bile acids, lipopolysaccharides (LPS). While microbiota's impact immune regulation, neuroinflammation, tumor development is well established, gaps remain grasping how specific contribute to neuro-cancer interactions. We discuss with potential implications for neurobiology cancer, indoles polyamines, which yet be extensively studied. Furthermore, we review preclinical clinical evidence linking dysbiosis, altered metabolite profiles, tumors, showcasing limitations research gaps, particularly human longitudinal studies. Case studies investigating microbiota-based interventions, including dietary changes, fecal transplantation, probiotics, demonstrate promise but also indicate hurdles translating these findings therapies. concludes call standardized multi-omics approaches bi-directional frameworks integrating microbiome, neuroscience, oncology develop personalized therapeutic strategies patients.

Language: Английский

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Neurobiological mechanisms in the kynurenine pathway and major depressive disorder

Reviews in the Neurosciences, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 5, 2024

Major depressive disorder (MDD) is a prevalent psychiatric that has damage to people's quality of life. Tryptophan the precursor serotonin, critical neurotransmitter in mood modulation. In mammals, most free tryptophan degraded by kynurenine pathway (KP), resulting range metabolites involved inflammation, immune response, and neurotransmission. The imbalance between quinolinic acid (QA), toxic metabolite, kynurenic (KynA), protective relevant phenomenon pathophysiology MDD. Proinflammatory cytokines increase activity enzyme indoleamine 2,3-dioxygenase (IDO), leading degradation KP an release QA. IDO activates proinflammatory genes, potentiating neuroinflammation deregulating other physiological mechanisms related chronic stress This review highlights with MDD, which are underlying discuss potential therapeutic targets.

Language: Английский

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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

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Interaction and regulation of the mitochondrial proteome – in health and disease

Expert Review of Proteomics, Journal Year: 2025, Volume and Issue: 22(1), P. 19 - 33

Published: Jan. 2, 2025

Introduction Mitochondria contain multiple pathways including energy metabolism and several signaling synthetic pathways. Mitochondrial proteomics is highly valuable for studying diseases inherited metabolic disorders, complex common disorders like neurodegeneration, diabetes cancer, since they all to some degree have mitochondrial underpinnings.

Language: Английский

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From Discrimination to Disease: The Role of Inflammation

Harvard Review of Psychiatry, Journal Year: 2025, Volume and Issue: 33(2), P. 83 - 89

Published: March 1, 2025

Abstract Discrimination is an established social determinant of mental health that contributes to psychiatric illness disparities among marginalized populations. There emerging research elucidating the biological mechanisms connecting discrimination outcomes, revealing inflammation as a key pathway. This column synthesizes evidence from existing literature on links between and inflammation, outlines both opportunities challenges in this field. The discussion highlights necessity multifaceted approach address discrimination, thus, reduce at individual population levels.

Language: Английский

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Exercise-induced adaptations in the kynurenine pathway: implications for health and disease management

Frontiers in Sports and Active Living, Journal Year: 2025, Volume and Issue: 7

Published: March 6, 2025

Background Tryptophan (TRP) metabolism through the kynurenine (KYN) pathway is influenced by inflammatory mediators, generating metabolites that regulate immune and responses. Exercise has been proposed as a modulator of this pathway, but its role in health benefits chronic disease management remains unclear. Objective This systematic review examines exercise-induced adaptations KYN their potential implications for management. Additionally, we identify key methodological considerations future research. Methods A structured search PubMed/Medline, Web Science, Scopus was conducted up to October 2024 clinical trials investigating effects exercise training on pathway. Results Of 2,795 articles initially found, 13 involving 592 participants met inclusion criteria. Most studies reported particularly cancer survivors. These appeared be intensity duration. However, several limitations were noted, no included patients with metabolic or cardiovascular diseases. Conclusions Here, show modulates both healthy diseased populations, highlighting prevention further randomized-controlled are needed clarify mechanisms applications, Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO/view/CRD42022351481 , PROSPERO (CRD42022351481).

Language: Английский

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