Anthranilic Acid–G-Protein Coupled Receptor109A–Cytosolic Phospholipase A2–Myelin–Cognition Cascade: A New Target for the Treatment/Prevention of Cognitive Impairment in Schizophrenia, Dementia, and Aging DOI Open Access
Gregory F. Oxenkrug

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(24), P. 13269 - 13269

Published: Dec. 10, 2024

Cognitive impairment is a core feature of neurodevelopmental (schizophrenia) and aging-associated (mild cognitive Alzheimer’s dementia) neurodegenerative diseases. Limited efficacy current pharmacological treatments warrants further search for new targets nootropic interventions. The breakdown myelin, phospholipids axonal sheath that protects the conduction nerve impulse between neurons, was proposed as neuropathological abnormality precedes promotes deposition amyloid-β in neuritic plaques. present review recent literature our own pre- clinical data suggest (for first time) anthranilic acid (AA)-induced activation microglial-expressed G-protein coupled receptor (GPR109A) inhibits cytosolic phospholipase A2 (cPLA2), an enzyme triggers degradation myelin consequently attenuates impairment. suggests up-regulation AA formation sex-specific compensatory (adaptive) reaction aimed to prevent/treat AA–GPR109A–cPLA2–myelin–cognition cascade interventions, e.g., administration pegylated kynureninase, catalyzes from Kynurenine (Kyn), tryptophane catabolite; interferon-alpha; central peripheral Kyn aminotransferase inhibitors increase availability substrate formation; vagus stimulation. predicts activity exogenous GPR109A agonists were designed underwent trials (unsuccessful) anti-dyslipidemia agents. might contribute pathogenesis Data on disorders are scarce, needs exploration studies

Language: Английский

Bridging gap in the treatment of Alzheimer’s disease via postbiotics: Current practices and future prospects DOI
Bushra Bashir, Monica Gulati, Sukriti Vishwas

et al.

Ageing Research Reviews, Journal Year: 2025, Volume and Issue: unknown, P. 102689 - 102689

Published: Feb. 1, 2025

Language: Английский

Citations

3
Postbiotics as Molecules Targeting Cellular Events of Aging Brain—The Role in Pathogenesis, Prophylaxis and Treatment of Neurodegenerative Diseases DOI Open Access

Pola Głowacka,

Katarzyna Oszajca, Agnieszka Pudlarz

et al.

Nutrients, Journal Year: 2024, Volume and Issue: 16(14), P. 2244 - 2244

Published: July 12, 2024

Aging is the most prominent risk factor for neurodegeneration occurrence. The common neurodegenerative diseases (NDs), Alzheimer’s (AD) and Parkinson’s (PD) diseases, are characterized by incidence of proteinopathy, abnormal activation glial cells, oxidative stress, neuroinflammation, impaired autophagy cellular senescence excessive patient’s age. Moreover, mitochondrial disfunction, epigenetic alterations neurogenesis inhibition, together with increased blood–brain barrier permeability gut dysbiosis, have been linked to ND pathogenesis. Since NDs still lack curative treatment, recent research has sought therapeutic options in restoring microbiota supplementing probiotic bacteria-derived metabolites beneficial action host—so called postbiotics. current review focuses on literature explaining mechanisms involved pathogenesis addressing impact that postbiotics as a whole mixture particular metabolites, such short-chain fatty acids (SCFAs), lactate, polyamines, polyphenols, tryptophan exopolysaccharides bacterial extracellular vesicles, ageing-associated processes underlying also discusses issue implementing into prophylaxis therapy, depicting them compounds senescence-triggered dysfunctions worth translating from bench pharmaceutical market response “silver consumers” demands.

Language: Английский

Citations

8
Anthranilic Acid, a GPR109A Agonist, and Schizophrenia DOI Open Access
Gregory F. Oxenkrug,

Brent P. Forester

International Journal of Tryptophan Research, Journal Year: 2024, Volume and Issue: 17

Published: Jan. 1, 2024

Introduction: Limited clinical efficiency of current medications warrants search for new antipsychotic agents. Deorphanized G-protein coupled receptor (GPR)109A has not attracted much attention schizophrenia researchers. We analyzed literature and our data on endogenous agonists GPR109A, beta-hydroxybutyrate (BHB), anthranilic (AA), butyric (BA), nicotinic (NA) acids, in individuals with schizophrenia. Data: Sex specific differences: plasma AA levels were 27% higher female than male patients correlated PANSS before 6 weeks antipsychotics treatment ( r = .625, P < .019, Spearman’s test). There was no sex differences after treatment. inversely (−.58, .005) scores responders to (at least, 50% improvement) but nonresponders. Preclinical studies suggested effect BHB BA. Clinical observed NA; benzoate sodium, an precursor; interventions associated upregulation (eg, fasting ketogenic diets). Discussion: Upregulation anti-inflammatory neuroprotective receptor, inhibits cytosolic phospholipase A2 (cPLA2), enzyme that breakdown myelin, lipid-based insulating axonal sheath protects promotes nerve conduction. Brain cPLA2 is upregulated subjects at high-risk development psychosis. Lower myelin content cognitive decline Therefore, GPR109A might exert via suppression cPLA2, and, consequently, preservation integrity. Future research explore effects (1) human pegylated kynureninase, catalyzes formation from kynurenine (Kyn); (2) inhibitors Kyn conversion into kynurenic acid, example, KYN5356, already impaired 3-hydroxykynurenine; (3) synthetic GPR 109A agonists, MK-1903 SCH900271 GSK256073, underwent trials as anti-dyslipidemia expression, be a endophenotype schizophrenia, especially impairment, needs thorough assessment.

Language: Английский

Citations

5
Exploring Therapeutic Potential of Phytoconstituents as a Gut Microbiota Modulator in the Management of Neurological and Psychological Disorders DOI

Prarit Chandel,

Komal Thapa, Neha Kanojia

et al.

Neuroscience, Journal Year: 2024, Volume and Issue: 551, P. 69 - 78

Published: May 14, 2024

Language: Английский

Citations

4
Early life imidacloprid and copper exposure affects the gut microbiome, metabolism, and learning ability of honey bees (Apis mellifera). DOI

Xi-Jie Li,

Qihe Tang,

Mengshang Hou

et al.

Environmental Research, Journal Year: 2025, Volume and Issue: unknown, P. 121134 - 121134

Published: Feb. 1, 2025

Language: Английский

Citations

0
Cellular Respiration and Amino Acid Metabolism Is Altered by Dietary Oligosaccharides inSalmonellaDuring Epithelial Association DOI Open Access
Claire Shaw, Poyin Chen,

Narine Arabyan

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 12, 2025

Abstract Dietary prebiotic oligosaccharides are common in people’s diets; however, little is known about how different prebiotics alter the enteric epithelium and microbiome. Here we show two structurally oligosaccharides, human milk (HMO) mannanoligosaccharides (MOS), metabolism of colonic epithelial cells Salmonella enterica sv. Typhimurium ways specific to each prebiotic. Initially, HMO MOS addition decreased S. association with cells. However, gene expression analysis revealed significantly induced Specific Pathogenicity Island (SPI) 1 2 treatment opposed increased fimbriae treatment. genes for amino acid both host Typhimurium, a metabolic shift that was not observed treated also altered respiration be more closely aligned those vivo during gut inflammation, which colonization-type HMO. Alteration virulence found dose dependent, indicating some dietary substrates likely pathogens change their potential unanticipated lead multiple outcomes potentiate or attenuate infections.

Language: Английский

Citations

0
Could a Mediterranean Diet Modulate Alzheimer’s Disease Progression? The Role of Gut Microbiota and Metabolite Signatures in Neurodegeneration DOI Creative Commons
Alice Njolke Mafe, Dietrich Büsselberg

Foods, Journal Year: 2025, Volume and Issue: 14(9), P. 1559 - 1559

Published: April 29, 2025

Neurodegenerative disorders such as Alzheimer’s disease (AD), the most common form of dementia, represent a growing global health crisis, yet current treatment strategies remain primarily palliative. Recent studies have shown that neurodegeneration through complex interactions within gut–brain axis largely depends on gut microbiota and its metabolites. This review explores intricate molecular mechanisms linking dysbiosis to cognitive decline, emphasizing impact microbial metabolites, including short-chain fatty acids (SCFAs), bile acids, tryptophan neuroinflammation, blood–brain barrier (BBB) integrity, amyloid-β tau pathology. The paper highlights major microbiome signatures associated with disease, detailing their metabolic pathways inflammatory crosstalk. Dietary interventions promise in modulating composition, potentially mitigating neurodegenerative processes. critically examines influence dietary patterns, Mediterranean Western diets, microbiota-mediated neuroprotection. Bioactive compounds like prebiotics, omega-3 polyphenols exhibit neuroprotective effects by reducing neuroinflammation. Furthermore, it discusses emerging microbiome-based therapeutic strategies, probiotics, postbiotics, fecal transplantation (FMT), potential for slowing progression. Despite these advances, several knowledge gaps remain, interindividual variability responses need large-scale, longitudinal studies. study proposes an integrative, precision medicine approach, incorporating science into paradigms. Ultimately, cognizance at mechanistic level could unlock novel avenues, offering non-invasive, diet-based strategy managing improving health.

Language: Английский

Citations

0
Biological studies reveal the role of trpA gene in biofilm formation, motility, hemolysis and virulence in Vibrio anguillarum DOI

Jinyuan Che,

Binghong Liu,

Qitong Fang

et al.

Microbial Pathogenesis, Journal Year: 2025, Volume and Issue: unknown, P. 107331 - 107331

Published: Jan. 1, 2025

Language: Английский

Citations

0
Kynurenine Pathway in Epilepsy: Unraveling Its Role in Glutamate Excitotoxicity, GABAergic Dysregulation, Neuroinflammation, and Mitochondrial Dysfunction DOI
Manpreet Kaur,

Pratyush Porel,

Ronak Y. Patel

et al.

Neurotoxicity Research, Journal Year: 2025, Volume and Issue: 43(2)

Published: March 28, 2025

Language: Английский

Citations

0
Decoding serotonin: the molecular symphony behind depression DOI Creative Commons

Yue Shu,

Lei Tian, Xing Wang

et al.

Frontiers in Cellular Neuroscience, Journal Year: 2025, Volume and Issue: 19

Published: April 24, 2025

The serotonin (5-hydroxytryptamine) system represents a crucial neurotransmitter network that regulates mood, behavior, and cognitive functions, playing significant role in the pathogenesis progression of depression. Although this perspective faces challenges, continues to exert substantial modulatory effects on specific aspects psychological functioning actively contributes multiple pathological processes depression development. Therefore, review systematically integrates interdisciplinary research advances regarding relationship between 5-hydroxytryptamine (5-HT) By focusing core biological including biosynthesis metabolism, SERT gene regulatory networks, protein molecular modifications, it aims elucidate how 5-HT dysregulation development depression, while providing novel perspectives therapeutic targets for innovative antidepressant drug

Language: Английский

Citations

0