Article
Urology & Nephrology
Vetalise C. Konje, Thekkelnaycke M. Rajendiran, Keith Bellovich, Crystal A. Gadegbeku, Debbie S. Gipson, Farsad Afshinnia, Anna Mathew
Summary: The study revealed that low tryptophan levels are associated with incident CVD in CKD. Additionally, increasing levels of tryptophan and kynurenine can improve the accuracy of predicting incident CVD using discriminant analysis.
CLINICAL KIDNEY JOURNAL
(2021)
Review
Medicine, Research & Experimental
Eslam E. Abd El-Fattah
Summary: Cancer is a leading cause of death globally. The change in the tumor immune microenvironment, specifically immunosuppression, is associated with cancer progression, metastasis, recurrence, and chemoresistance. Indoleamine 2,3-dioxygenase (IDO) and its metabolite kynurenine (Kyn) play a significant role in the immunosuppression of lung cancer.
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
Article
Geriatrics & Gerontology
Gonja Javani, Shirin Babri, Fereshteh Farajdokht, Arshad Ghaffari-Nasab, Gisou Mohaddes
Summary: This study aimed to determine the effects of mitotherapy on learning and memory and hippocampal kynurenine (Kyn) pathway, mitochondria function, and dendritic arborization and spines density in aged rats subjected to chronic mild stress. The results showed that mitotherapy markedly improved both spatial and episodic memories in the Aged + Stress + Mit group compared to the Aged + Stress. Moreover, mitotherapy decreased IDO protein expression and activity and Kyn levels, while it increased ATP levels and improved MMP in the hippocampus of the Aged + Stress + Mit group. Besides, mitotherapy restored dendritic atrophy and loss of spine density in the hippocampal neurons of the stress-exposed aged rats.
Review
Immunology
Florent Peyraud, Jean-Philippe Guegan, Dominique Bodet, Sophie Cousin, Alban Bessede, Antoine Italiano
Summary: Metabolism of tryptophan plays a crucial role in tumor malignancy and immune suppression, making it a potential target for cancer immunotherapy. While IDO1 inhibitors have shown promising preclinical data, their effectiveness in clinical trials has been questioned, highlighting the complexity of combinatorial approaches. This review explores the immunomodulatory role of tryptophan catabolism metabolites, discusses the shortcomings of IDO1 inhibitors in clinical trials, and examines alternative approaches in the field of immunotherapy.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Emina Sudar-Milovanovic, Zoran Gluvic, Milan Obradovic, Bozidarka Zaric, Esma R. Isenovic
Summary: This article reviews the link between mammalian tryptophan metabolism and its role in atherosclerosis and diabetes, and outlines intervention strategies.
CURRENT MEDICINAL CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Tanveer Singh, Rajesh Kumar Goel
Summary: Depression is a common psychiatric comorbidity associated with epilepsy, impacting the patient's quality of life. Selective serotonin reuptake inhibitors (SSRIs) and selective serotonin and norepinephrine reuptake inhibitors (SNRIs) are considered first-line antidepressants for people with epilepsy, although there is a lack of high-quality evidence to support this.
NEUROCHEMICAL RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Hui Phing Ang, Suzana Makpol, Muhammad Luqman Nasaruddin, Nurul Saadah Ahmad, Jen Kit Tan, Wan Asyraf Wan Zaidi, Hashim Embong
Summary: This study examined the role of IDO and TRP-KP in lipopolysaccharide-induced delirium in a chronic cerebral hypoperfusion model. The results showed that LPS treatment led to behavior deficits and increased IDO expression, suggesting a potential therapeutic target for delirium.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Oncology
Trevor W. Stone, Richard O. Williams
Summary: This review focuses on the role of tryptophan metabolism in inflammation and cancer development, particularly the impact of kynurenine and related compounds. It proposes targeting the kynurenine pathway to indirectly affect interacting pathways and potentially modify tryptophan metabolism. The study provides insights into the relationship between inflammation and cancer, and suggests alternative drug targets.
Article
Chemistry, Medicinal
Juyoung Jung, Hongchul Yoon, Te-ik Sohn, Kyusic Jang, Yeongran Yoo, Ilji Jeong, Jae Eui Shin, Jin Hee Lee, Jihyae Ann, Jeewoo Lee
Summary: Through a structure-activity relationship study, the N-3-bromophenyl derivative 19 was identified as the most potent inhibitor of IDO1, with an IC50 value of 0.44 μM. Molecular modeling revealed that interactions with heme iron, halogen bonding with Cys129, and hydrophobic interactions were crucial for the high potency of compound 19.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Review
Chemistry, Medicinal
Rahul Singh, Deepak B. Salunke
Summary: IDO1 enzyme catalyzes the initial step of kynurenine pathway and is implicated in immune modulation, antioxidation, and cancer progression. Overexpression of IDO1 plays a pivotal role in immune evasion and cancer development. Research and development of IDO1 inhibitors holds significant potential in immunotherapy and disease treatment.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Arshad Ghaffari-Nasab, Reza Badalzadeh, Gisou Mohaddes, Gonja Javani, Abbas Ebrahimi-kalan, Mohammad Reza Alipour
Summary: The pathophysiology of depression in the elderly is linked to age-related changes in IDO levels and activity, as well as Kyn metabolites. Young plasma shows promising antidepressant effects in aged rats under stress, improving behavioral symptoms and reducing key biomarkers in the prefrontal cortex.
NEUROCHEMICAL RESEARCH
(2022)
Article
Multidisciplinary Sciences
Ott Kiens, Egon Taalberg, Viktoria Ivanova, Ketlin Veevali, Triin Laurits, Ragne Tamm, Aigar Ottas, Kalle Kilk, Ursel Soomets, Alan Altraja
Summary: The study found significant alterations in serum profiles of amino acid and biogenic amines in patients with OSA compared to controls, suggesting vast pathophysiologic shifts reflected in the systemic metabolism. Significant elevations in alanine, proline, and kynurenine concentrations in OSA patients were detected, as well as changes in overnight dynamics of other amino acids.
SCIENTIFIC REPORTS
(2021)
Article
Pharmacology & Pharmacy
Katarzyna Ciapala, Katarzyna Pawlik, Agata Ciechanowska, Joanna Mika, Ewelina Rojewska
Summary: Changes in the kynurenine pathway enzymes and metabolites were investigated in a chronic constriction injury (CCI) model of neuropathic pain in mice. Modulation of the kynurenine pathway through pharmacological interventions attenuated mechanical and thermal hypersensitivity in mice with neuropathic pain and enhanced the effectiveness of selected opioids. The injection of L-kynurenine preceded by a KMO inhibitor was found to be particularly effective in reducing hypersensitivity. Furthermore, L-kynurenine exerted an analgesic effect when administered intravenously, which was enhanced by a microglial activation inhibitor. Overall, the results suggest that modulation of the kynurenine pathway may be a promising pharmacological approach to managing neuropathy.
TOXICOLOGY AND APPLIED PHARMACOLOGY
(2023)
Review
Pharmacology & Pharmacy
Ying Tan, Miaomiao Liu, Ming Li, Yujuan Chen, Meng Ren
Summary: L-tryptophan metabolism is involved in the regulation of various physiological processes. Inhibiting the enzyme IDO1, which catalyzes the conversion of tryptophan, has therapeutic benefits for several diseases. Natural compounds, such as quinones, polyphenols, alkaloids, and others, have been found to have inhibitory activity against IDO1 and can be further optimized for potential use as IDO1 inhibitors.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Ruta Zulpaite, Povilas Miknevicius, Bettina Leber, Kestutis Strupas, Philipp Stiegler, Peter Schemmer
Summary: Solid organ transplantation faces challenges such as organ shortage, extended criteria donor organs, and immune regulation issues with a lack of accurate biomarkers for predicting dysfunction and rejection. Tryptophan and its metabolites are of interest in this field, offering therapeutic and prognostic potential.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Irene L. Gutierrez, Cinzia Dello Russo, Fabiana Novellino, Javier R. Caso, Borja Garcia-Bueno, Juan C. Leza, Jose L. M. Madrigal
Summary: This article summarizes the role of noradrenaline in Alzheimer's disease and suggests the use of noradrenaline-modulating drugs as a therapeutic option.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Irene L. Gutierrez, Fabiana Novellino, Javier R. Caso, Borja Garcia-Bueno, Juan C. Leza, Jose L. M. Madrigal
Summary: The chemokine CCL2 plays a role in neuroinflammatory processes by recruiting glial cells and also inhibiting resolution of inflammation in astrocytes, which may contribute to the progression of neuroinflammatory processes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
David Martin-Hernandez, Irene L. Gutierrez, Marta Gonzalez-Prieto, Karina S. MacDowell, Javier Robledo-Montana, Hiram Tendilla-Beltran, Natalia Calleja-Rodriguez, Alvaro G. Bris, Cristina Ulecia-Moron, Beatriz Moreno, Javier R. Caso, Borja Garcia-Bueno, Sandra Rodrigues-Mascarenhas, Ignacio Marin-Jimenez, Juan Carlos Leza, Luis Menchen
Summary: The chronic inflammatory process in inflammatory bowel diseases (IBD) is mainly driven by T-cell response to microbial and environmental antigens. Psychological stress can trigger clinical flares of IBD, and sphingosine-1-phosphate (S1P) is involved in T-cell recruitment. By evaluating the impact of stress and the absence of sphingosine kinase 2 (Sphk2) on the colon of mice, it was found that stress increased S1P levels in the colon, possibly due to decreased degradation enzymes and Sphk2. This S1P accumulation could lead to inflammation and immune dysregulation, contributing to the development of IBD.
SCIENTIFIC REPORTS
(2022)
Article
Psychiatry
Maria Garcia-Lopez, Miguel Alonso-Sanchez, Itziar Leal, David Martin-Hernandez, Javier R. Caso, Covadonga M. Diaz-Caneja, Alvaro Andreu-Bernabeu, Celso Arango, Roberto Rodriguez-Jimenez, Luis Sanchez-Pastor, Marina Diaz-Marsa, Blanca Mellor-Marsa, Angela Ibanez, Norberto Malpica, Maria-Fe Bravo-Ortiz, Enrique Baca-Garcia, Jose Luis Ayuso-Mateos, Ana Izquierdo
Summary: This study examines the relationships between social cognition, social functioning, and negative symptoms in first-episode psychosis patients. The findings suggest a direct relationship between social cognition and social functioning, with an indirect connection mediated by the experiential factor of negative symptoms.
JOURNAL OF PSYCHIATRIC RESEARCH
(2022)
Article
Clinical Neurology
Valeria Sacca, Fabiana Novellino, Maria Salsone, Maurice Abou Jaoude, Andrea Quattrone, Carmelina Chiriaco, Jose L. M. Madrigal, Aldo Quattrone
Summary: This study aimed to investigate the applicability of machine learning on resting-state fMRI connectivity data for detecting functional changes in essential tremor (ET). A support vector machine with a radial kernel was trained on the average signals from 14 brain networks obtained from ET and healthy control subjects. The machine learning algorithm achieved an AUC of 0.75 and identified four networks (language, primary visual, cerebellum, and attention), which have significant roles in ET pathophysiology, as the most important features for classification. Univariate analysis could not find significant results between the two conditions.
NEUROLOGICAL SCIENCES
(2023)
Editorial Material
Pharmacology & Pharmacy
Marta P. Pereira, Borja Garcia-Bueno, Javier R. Caso
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Macarena Calero, Lara H. Moleiro, Aline Sayd, Yeray Dorca, Lluis Miquel-Rio, Veronica Paz, Javier Robledo-Montana, Eduardo Enciso, Fernando Accion, Diego Herraez-Aguilar, Thomas Hellweg, Luis Sanchez, Analia Bortolozzi, Juan C. Leza, Borja Garcia-Bueno, Francisco Monroy
Summary: This study presents a colloidal synthesis method for integrating DNA antisense oligonucleotides into lipid nanoparticles, which can be used for the treatment of neuroinflammation-related diseases. The nanoparticles are functionalized to target brain border-associated macrophages and silence specific genes. The results provide a novel approach for gene therapy in neuroinflammation-related diseases.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Dentistry, Oral Surgery & Medicine
David Martin-Hernandez, Maria Martinez, Javier Robledo-Montana, Marina Munoz-Lopez, Leire Virto, Nagore Ambrosio, Maria Jose Marin, Eduardo Montero, David Herrera, Mariano Sanz, Juan C. Leza, Elena Figuero, Borja Garcia-Bueno
Summary: This study investigated the potential mechanisms underlying the association between periodontitis and depression. Using a rat model, the study found that neuroinflammation (microglia, blood-brain barrier permeability, and sphingosine-1-phosphate pathways) may play a role in this association. The findings showed that the combined effects of periodontitis and chronic mild stress increased neuroinflammation and disrupted the blood-brain barrier. The study also identified differential regulation of enzymes and receptors in the sphingosine-1-phosphate pathway. These findings contribute to our understanding of the relationship between periodontitis and depression.
JOURNAL OF CLINICAL PERIODONTOLOGY
(2023)
Editorial Material
Pharmacology & Pharmacy
Marta P. Pereira, Borja Garcia-Bueno, Javier R. Caso
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Multidisciplinary Sciences
Fernando Garcia-Dolores, Hiram Tendilla-Beltran, Francisco Flores, Linda Alejandra Carbajal-Rimoldi, Roberto Cuauhtemoc Mendoza-Morales, Laura Erendira Gomez-Mendoza, Andrea Judith Vazquez-Hernandez, Fidel de la Cruz, Alma Delia Genis-Mendoza, Humberto Nicolini, Gonzalo Flores
Summary: The suicide rate in Mexico City increased during the COVID-19 pandemic, particularly in the first half of 2020. This increase was observed across all age groups, but young people aged 15-24 had the highest suicide rate. The main cause of suicide was depression. These findings highlight the need for new prevention and care strategies.
Review
Endocrinology & Metabolism
Agueda Castro-Quintas, Helena Palma-Gudiel, Nerea San Martin-Gonzalez, Javier R. Caso, Juan C. Leza, Lourdes Fananas
Summary: Mucosal secretory immunoglobulin A (s-IgA) is an important component of human first line defense. This review investigates the reactivity of s-IgA to psychosocial stress in subjects under the age of 18. The findings suggest that s-IgA levels increase in children older than 9 years old when exposed to stress, and that s-IgA follows a circadian rhythm which is altered under stress conditions. These results indicate that s-IgA could be a potential psychosocial stress biomarker in pediatric and child-juvenile psychiatric populations, although further studies are needed to validate its role.
FRONTIERS IN NEUROENDOCRINOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Gabriel D. Flores-Gomez, David Javier Apam-Castillejos, Ismael Juarez-Diaz, Estefania Fuentes-Medel, Alfonso Diaz, Hiram Tendilla-Beltran, Gonzalo Flores
Summary: This study evaluated the effects of the atypical antipsychotic aripiprazole on behavioral and neuronal disturbances in the medial prefrontal cortex of rats with neonatal ventral hippocampus lesion. The results showed that aripiprazole attenuated hyperlocomotion and improved structural neuroplasticity disturbances in the layer 3 pyramidal cells of the medial prefrontal cortex. These effects may be mediated by increased levels of brain-derived neurotrophic factor.
JOURNAL OF CHEMICAL NEUROANATOMY
(2023)
Review
Biochemistry & Molecular Biology
David Martin-Hernandez, Marina Munoz-Lopez, Hiram Tendilla-Beltran, Javier R. Caso, Borja Garcia-Bueno, Luis Menchen, Juan C. Leza
Summary: Extensive research has shown the importance of immune alterations and dysfunctional biological barriers in psychiatric disorders. The leaky gut phenomenon, closely related to the brain and intestinal barriers, may contribute to inflammation in these conditions. Drugs based on sphingosine-1-phosphate (S1P), such as fingolimod and ozanimod, have been approved for multiple sclerosis and ulcerative colitis treatment, sparking a debate for their use in psychiatry. This review focuses on the molecular mechanisms of S1P in modulating the immune system and brain/intestinal barriers, aiming to uncover innovative therapies for psychiatric diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
