The Underlying Neurobiological Mechanisms of Psychosis: Focus on Neurotransmission Dysregulation, Neuroinflammation, Oxidative Stress, and Mitochondrial Dysfunction

Antioxidants, Journal Year: 2024, Volume and Issue: 13(6), P. 709 - 709

Published: June 12, 2024

Psychosis, defined as a set of symptoms that results in distorted sense reality, is observed several psychiatric disorders addition to schizophrenia. This paper reviews the literature relevant underlying neurobiology psychosis. The dopamine hypothesis has been major influence study neurochemistry psychosis and development antipsychotic drugs. However, it became clear early on other factors must be involved dysfunction In current review, reported how these factors, namely dysregulation neurotransmitters [dopamine, serotonin, glutamate, γ-aminobutyric acid (GABA)], neuroinflammation, glia (microglia, astrocytes, oligodendrocytes), hypothalamic–pituitary–adrenal axis, gut microbiome, oxidative stress, mitochondrial contribute interact with one another. Research increased knowledge complexity psychotic disorders. Potential new pharmacotherapies, including combinations drugs (with pre- probiotics some cases) affecting mentioned above, have suggested. Similarly, putative biomarkers, particularly those related immune system, proposed. Future research both pharmacotherapy biomarkers will require better-designed studies conducted an all stages consider confounders such sex differences comorbidity.

Language: Английский

---

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

---

The role of kynurenines in migraine-related neuroimmune pathways

The Journal of Headache and Pain, Journal Year: 2024, Volume and Issue: 25(1)

Published: Aug. 6, 2024

Abstract Migraine, a primary headache disorder whose mechanism remains incompletely understood, appears to involve the activation of trigeminovascular system (TS) during attacks. Research suggests that inflammatory processes mediated by immune may play role in migraine pathophysiology. Neuroinflammation is often associated with attacks, cytokines serving as crucial mediators process. Elevated levels pro-inflammatory cytokines, such interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), have been observed blood cerebrospinal fluid individuals experiencing These capacity sensitize pain pathways brain, thereby increasing sensitivity stimuli. This phenomenon, known central sensitization, believed contribute intensity persistence pain. Kynurenines, endogenous glutamatergic mechanisms, can significantly influence pathophysiology disorders. The kynurenine collectively pathway (KP), which act on multiple receptors, glutamate aryl hydrocarbon receptors (AhRs), G protein-coupled 35 (GPR35), α-7 nicotinic acetylcholine (α7 nACh) receptors. are also found various cells system, so KP pathomechanism headaches be through them. In this review, our goal show possible link between context inflammation migraine. Migraine research recent years has focused neuropeptides, calcitonin gene-related peptide (CGRP) pituitary adenylate cyclase-activating polypeptide (PACAP) potential pathogenic factors therapeutic approaches. peptides share many similarities their characteristics roles. For instance, they exhibit potent vasodilation, occur both peripheral nervous systems, transmitting nociception neurogenic inflammation. investigation connections aforementioned neuropeptides could significant uncovering identifying new drug candidates.

Language: Английский

---

The Biology and Biochemistry of Kynurenic Acid, a Potential Nutraceutical with Multiple Biological Effects

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(16), P. 9082 - 9082

Published: Aug. 21, 2024

Kynurenic acid (KYNA) is an antioxidant degradation product of tryptophan that has been shown to have a variety cytoprotective, neuroprotective and neuronal signalling properties. However, mammalian transporters receptors display micromolar binding constants; these are consistent with its typically tissue concentrations but far above serum/plasma concentration (normally tens nanomolar), suggesting large gaps in our knowledge transport mechanisms action, the main influx characterized date equilibrative, not concentrative. In addition, it substrate known anion efflux pump (ABCC4), whose vivo activity largely unknown. Exogeneous addition L-tryptophan or L-kynurenine leads production KYNA also many other co-metabolites (including some such as 3-hydroxy-L-kynurenine quinolinic may be toxic). With exception chestnut honey, exists at relatively low levels natural foodstuffs. bioavailability reasonable, terminal element irreversible reaction most pathways, might added exogenously without disturbing upstream metabolism significantly. Many examples, which we review, show valuable bioactivity. Given above, review potential utility nutraceutical, finding significantly worthy further study development.

Language: Английский

---

Aloe Emodin Alleviates Radiation‐Induced Heart Disease via Blocking P4HB Lactylation and Mitigating Kynurenine Metabolic Disruption

Advanced Science, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 4, 2024

Abstract Aloe emodin is an anthraquinone of traditional Chinese medicine monomer, which plays a protective action in cardiovascular diseases. However, the regulatory mechanisms aloe protection radiation‐induced heart damage (RIHD) are unclear. As novel post‐translational modification, lactylation considered as critical mediator inflammatory cascade and cardiac injury. Here, using cross differential omics 4D label‐free omics, protein disulfide‐isomerase (P4HB) identified target for lactylation, inhibits binding lactate to K311 site P4HB. stabilizes kynurenine metabolism through inhibition aspartate aminotransferase (GOT2) accumulation on damaged mitochondria. Mechanistically, phosphorylated glycogen synthase kinase 3B (p‐GSK3B) transcription nucleus repress interaction prostaglandin G/H 2 (PTGS2) with SH3 domain domain‐containing GRB2‐like B1 (SH3GLB1), thereby disrupting functions mitochondrial complexes reducing SH3GLB1‐mediated mitoROS accumulation, eventually suppressing calcium‐binding coiled‐coil (NDP52)‐induced mitophagy. This study unveils role RIHD alleviation PTGS2/SH3GLB1/NDP52 axis, indicates GOT2‐mediated P4HB lactylation. Collectively, this provides insights into underlying injury, opens new avenues therapeutic strategies preventing by regulating

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

---

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

---

Dietary live microorganisms and depression-driven mortality in hypertensive patients: NHANES 2005–2018

Journal of Health Population and Nutrition, Journal Year: 2025, Volume and Issue: 44(1)

Published: April 13, 2025

To investigate the relationship between dietary microorganism intake and mortality risk among hypertensive adults with depression in United States. This study utilizes data from 2005-2018 National Health Nutrition Examination Survey, focusing on individuals hypertension. The Kaplan-Meier (K-M) curve is employed to preliminarily explore intake, depression, individuals. Cox proportional hazards model used for both individual combined analyses of these relationships. Mediation analysis assesses mediating effect association microorganisms mortality, while subgroup sensitivity evaluates stability model. cohort included 11,602 participants (5,904 men 5,698 women), 1,201 having depression. During follow-up period, 2,085 died all causes, 692 due cardiovascular events. Preliminary using K-M reveals that higher those without have lower risks. shows increased associated reduced (HRALL-cause=0.654, 95%CI: 0.555-0.771; HRCVD-cause:0.675, 0.472,0.967). High diets rich may mitigate ALL-cause populations(HRALL-cause=0.493, 0.256-0.947). revealed serves as a partial mediator process improving long - term prognosis population. Results showed beneficial remained stable most Patients suffering hypertension can reduce all-cause caused by increasing their microorganisms. provides clinicians new non-pharmacological intervention approach offers direction optimization clinical treatment regimens.

Language: Английский

---

The Connection Between the Oral Microbiota and the Kynurenine Pathway: Insights into Oral and Certain Systemic Disorders

Current Issues in Molecular Biology, Journal Year: 2024, Volume and Issue: 46(11), P. 12641 - 12657

Published: Nov. 7, 2024

The oral microbiome, comprising bacteria, fungi, viruses, and protozoa, is essential for maintaining both systemic health. This complex ecosystem includes over 700 bacterial species, such as

Language: Английский

---

Exploring the Role of Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) and Kynurenine Pathway Dysregulation in Migraine Pathophysiology Among Women With Polycystic Ovary Syndrome (PCOS)

Cureus, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 10, 2024

A narrative review was undertaken to explore the current understanding of relationship between polycystic ovary syndrome and migraine headaches, with a focus on potential roles pituitary adenylate cyclase-activating polypeptide kynurenine pathway in shared pathophysiology these conditions. Emerging evidence suggests that may be key player development implications for higher incidence observed women syndrome. Additionally, dysregulation altered levels metabolites have been linked both syndrome, indicating complex interplay hormonal, metabolic, neurological factors comorbid presentation disorders. Further research is needed elucidate specific mechanisms underlying associations develop targeted therapeutic approaches managing context

Language: Английский

---