Systematic Insights into the Relationship between the Microbiota–Gut–Brain Axis and Stroke with the Focus on Tryptophan Metabolism DOI Creative Commons
Xinyu Shen,

Xiaoqin Mu

Metabolites, Journal Year: 2024, Volume and Issue: 14(8), P. 399 - 399

Published: July 24, 2024

Stroke, as a serious cerebral vascular disease with high incidence and rates of disability mortality, has limited therapeutic options due to the narrow time window. Compelling evidence highlighted significance gut microbiota gut-brain axis critical regulatory factors affecting stroke. Along microbiota-gut-brain axis, tryptophan metabolism further acquires increasing attention for its intimate association central nervous system diseases. For purpose exploring potential role in stroke providing systematic insights into intricate connection pathological procedure stroke, this review first summarized practical relationship between by compiling latest case-control research. Then, well interaction were comprehensively elucidated on basis basic anatomical structure physiological function. Based crosstalk microbiota-gut-brain, we focused from three major metabolic pathways, namely, kynurenine pathway, serotonin microbial within axis. Moreover, effects appreciated elaborated here, which is scarcely found other reviews. Hopefully, illustration mechanisms pathways along will inspire more translational research perspectives, paid promising pharmaceutical target order reduce risk mitigate progression, ameliorate prognosis.

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

2
Neuroactive Kynurenines as Pharmacological Targets: New Experimental Tools and Exciting Therapeutic Opportunities DOI
Ana Pocivavsek, Robert Schwarcz, Sophie Erhardt

et al.

Pharmacological Reviews, Journal Year: 2024, Volume and Issue: 76(6), P. 978 - 1008

Published: Sept. 20, 2024

Both preclinical and clinical studies implicate functional impairments of several neuroactive metabolites the kynurenine pathway (KP), major degradative cascade essential amino acid tryptophan in mammals, pathophysiology neurologic psychiatric diseases. A number KP enzymes, such as 2,3-dioxygenase (TDO2), indoleamine 2,3-dioxygenases (IDO1 IDO2), aminotransferases (KATs), 3-monooxygenase (KMO), 3-hydroxyanthranilic oxygenase (3-HAO), quinolinic phosphoribosyltransferase (QPRT), control brain metabolism health disease are therefore increasingly considered to be promising targets for treatment disorders nervous system. Understanding distribution, cellular expression, regulation enzymes is critical conceptualization implementation successful therapeutic strategies. SIGNIFICANCE STATEMENT: Studies have implicated Key regulate both disease, making them treating these disorders. Therefore, understanding developing effective This review endeavors describe processes detail.

Language: Английский

Citations

9
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
The Biology and Biochemistry of Kynurenic Acid, a Potential Nutraceutical with Multiple Biological Effects DOI Open Access
Luana de Fátima Alves, J. Bernadette Moore, Douglas B. Kell

et al.

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

Citations

6
Gut microbial metabolism in Alzheimer's disease and related dementias DOI Creative Commons
Jea Woo Kang,

Vaibhav BV Vemuganti,

Jessamine F. Kuehn

et al.

Neurotherapeutics, Journal Year: 2024, Volume and Issue: 21(6), P. e00470 - e00470

Published: Oct. 1, 2024

Multiple studies over the last decade have established that Alzheimer's disease and related dementias (ADRD) are associated with changes in gut microbiome. These alterations organismal composition result abundances of functions encoded by microbial community, including metabolic capabilities, which likely impact host mechanisms. Gut microbes access dietary components other molecules made produce metabolites can enter circulation cross blood-brain barrier (BBB). In recent years, several been or shown to influence pathways relevant ADRD pathology. include short chain fatty acids, secondary bile tryptophan derivatives (such as kynurenine, serotonin, tryptamine, indoles), trimethylamine/trimethylamine N-oxide. Notably, some these BBB various effects on brain, modulating release neurotransmitters neuronal function, inducing oxidative stress inflammation, impacting synaptic function. Microbial also central nervous system through immune, enteroendocrine, enteric pathways, perturbations turn function peripheral immune responses, well integrity, homeostasis neurogenesis, glial cell maturation activation. This review examines evidence supporting notion is influenced microbiota its metabolites. The potential therapeutic advantages for preventing treating discussed, highlighting their role developing new treatments.

Language: Английский

Citations

6
Redefining Roles: A Paradigm Shift in Tryptophan–Kynurenine Metabolism for Innovative Clinical Applications DOI Open Access
Masaru Tanaka,

Ágnes Szabó,

László Vécsei

et al.

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

Citations

4
Role of Kynurenine and Its Derivatives in Liver Diseases: Recent Advances and Future Clinical Perspectives DOI Open Access
Qi-Wen Tan, Shenghe Deng, Lijuan Xiong

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 968 - 968

Published: Jan. 24, 2025

Liver health is integral to overall human well-being and the pathogenesis of various diseases. In recent years, kynurenine its derivatives have gradually been recognized for their involvement in pathophysiological processes, especially regulation liver diseases, such as acute injury, non-alcoholic fatty disease, cirrhosis, cancer. Kynurenine are derived from tryptophan, which broken down by enzymes indoleamine 2,3-dioxygenase (IDO) tryptophan (TDO), converting essential amino acid into (KYN) other downstream metabolites, kynurenic (KYNA), 3-hydroxykynurenine (3-HK), xanthurenic (XA), quinolinic (QA). can promote activity transcription factor aryl hydrocarbon receptor (AhR), suppress T cell immune modulation, inhibit activation inflammatory signaling pathways, NF-κB anti-inflammatory effects, hepatic stellate cells slow fibrosis progression. Additionally, metabolites influence progression diseases modulating gut microbiota. Therefore, this review, we summarize explore mechanisms regulate help develop new diagnostic or prognostic biomarkers effective therapies targeting pathway disease treatment.

Language: Английский

Citations

0
Systematic Insights into the Relationship between the Microbiota–Gut–Brain Axis and Stroke with the Focus on Tryptophan Metabolism DOI Creative Commons
Xinyu Shen,

Xiaoqin Mu

Metabolites, Journal Year: 2024, Volume and Issue: 14(8), P. 399 - 399

Published: July 24, 2024

Stroke, as a serious cerebral vascular disease with high incidence and rates of disability mortality, has limited therapeutic options due to the narrow time window. Compelling evidence highlighted significance gut microbiota gut-brain axis critical regulatory factors affecting stroke. Along microbiota-gut-brain axis, tryptophan metabolism further acquires increasing attention for its intimate association central nervous system diseases. For purpose exploring potential role in stroke providing systematic insights into intricate connection pathological procedure stroke, this review first summarized practical relationship between by compiling latest case-control research. Then, well interaction were comprehensively elucidated on basis basic anatomical structure physiological function. Based crosstalk microbiota-gut-brain, we focused from three major metabolic pathways, namely, kynurenine pathway, serotonin microbial within axis. Moreover, effects appreciated elaborated here, which is scarcely found other reviews. Hopefully, illustration mechanisms pathways along will inspire more translational research perspectives, paid promising pharmaceutical target order reduce risk mitigate progression, ameliorate prognosis.

Language: Английский

Citations

1