Featured Articles

The role of tryptophan metabolism in aging and longevity has been an ongoing and intriguing topic. One end product of tryptophan metabolism, NAD, has been a major focus in the study of aging and longevity. However, recent years have brought forth emerging evidence suggesting that other metabolites of the kynurenine pathway (KP) may also play a crucial role in aging and longevity. For example, metabolites of the KP have been linked to use as predictors of biological age, frailty (see April 2023 highlight), and Alzheimer’s Disease (see June 2022 highlight). These clinical findings underscore a strong motivation to delve deeper... read more

The COVID-19 pandemic has had lasting effects, and many individuals are still suffering from post-COVID syndrome (PCS). Patients suffering from PCS can have a wide range of symptoms including fatigue, shortness of breath, heart palpitations, “brain fog”, headache, depression, and/or anxiety. PCS can affect individuals for months or years, and it remains to be seen if some individuals will have life-long effects from COVID-19. Therefore, it is important to understand the underlying pathophysiology of PCS and identify potential therapeutic targets to lessen or resolve the symptoms of PCS. PCS has marked similarities with chronic fatigue syndrome (listen to the keynote... read more

ISTRY has been covering the advancements in knowledge around tryptophan metabolism and COVID-19 since our newsletter in 2021. We have provided ongoing updates in our Featured Article series (from August 2022 and June/July 2023) which have highlighted the duality of tryptophan catabolites; quinolinic acid (QA) has been implicated in long-covid, and picolinic acid (PA) has broad-spectrum antiviral properties in in-vivo models. There is now new evidence from Wong et al. 2023, from the University of Pennsylvania, Philadelphia, that implicates peripheral serotonin deficiency in the post-viral sequelae of “long COVID”.  Metabolomic analysis in long COVID patients, acute COVID patients, and fully recovered COVID patients revealed evidence... read more

Major depressive disorder (MDD) is one of the most prominent psychiatric disorders, as well as one of the most disabling. In some cases, MDD can lead to suicide which is a major global problem. Current antidepressant treatments targeting serotonin and norepinephrine brain signalling pathways are not effective in all cases of depression and they have significant limitations as it can take weeks to develop beneficial mood-enhancing effects. The limited understanding of MDD pathophysiology at a molecular level has been a major setback in the development of more effective treatment targets. Evidence suggests that alterations in the kynurenine pathway contribute to... read more

While dysregulation of the kynurenine pathway (KP) has been associated with pathogenesis, a complete loss of the KP can also have detrimental effects. For example, inhibiting indoleamine 2,3-dioxygenase (IDO)-1 during pregnancy results in fetal loss in a mouse model, which is likely driven by the loss of maternal immune tolerance. Furthermore, KP metabolites may also play a role in fetal development, kynurenic acid has been shown to be involved in neural plasticity and brain development. Since maternal kynurenine levels can impact the developing fetus, Dr. Bruno Pedraz-Petrozzi and colleagues recently investigated tryptophan and KP metabolite levels in the placenta, umbilical cord,... read more

Apart from its structural role that confers metal chelating properties, picolinic acid has been known to play vital roles against neurotoxicity, osteoporosis, and depression. Over the years, picolinic acid has shown to exhibit antiviral activity. The recent pandemic has placed the kynurenine pathway in the spotlight, as we previously covered details in our Newsletter issue 1, and more recently, it has been implicated in long COVID, as described in our featured article (see 2022 August issue). Now, we have further evidence that picolinic acid may play an important role against COVID. Narayan et al showed that picolinic acid is a... read more

Psychotic disorders are mental illnesses with psychosis, which includes schizophrenia. It can often be difficult to pinpoint the underlying disorder due to symptom overlap and being confounded by the patient’s delusional mindset. In order to identify at-risk patients, researchers have been investigating potential biomarkers. This work has primarily been focused on blood biomarkers, as these samples are easily obtained. However, it is appreciated that the changes in the blood biochemistry do not always reflect the changes in the brain biochemistry. Therefore, it is important to identify changes in the brain biochemistry of individuals with psychotic disorders, as this may be... read more

Frailty is a state in geriatrics where individuals have age-associated decline and increased vulnerability to multiple physiological systems. Individuals with neuromuscular function decline with associated sarcopenia have a greater incidence of hip fractures, increasing their risk of death. Recent studies have shown kynurenine pathway alterations in other age-related diseases including neurodegenerative disorders. Therefore, it is not surprising that frail adults also have alterations in KP metabolite levels including increased 3-hydroxykynurenine (3-HK) and quinolinic acid (QUIN) (Westbrook et al., 2020). You can learn more about the kynurenine pathway and frailty from one of our previous keynote speakers, Prof Gustavo Duque in... read more

The tryptophan research community is well aware that the kynurenine pathway contributes to the pathophysiology of neurodegeneration and cancer immunology. In the case of neurodegeneration, the chronic activation of the pathway leading to the production of neuroactive metabolites such as quinolinic acid (QA) has been known to propagate excitotoxicity across several neurodegenerative diseases. In the field of cancer immunology, the Indoleamine 2,3-dioxygenase-1-kynurenine-aryl hydrocarbon receptor (IDO1-kyn-AhR) axis has been a significant target for cancer immunotherapy. The paper highlighted in this feature article focuses on the NMDA agonist QA in cancer immunology, revealing a new role for QA in immuno-oncology. Kesarwani et al.... read more

Inflammatory bowel disease (IBD) affects nearly 7 million individuals worldwide and includes cases of Chrohn’s Disease and ulcerative colitis. This chronic inflammatory disorder affects the gastrointestinal tract. While the exact cause of the disease remains to be elucidated, there seems to be environmental risk factors, such as gut microbiome alterations, that are associated with IBD. Alterations in the gut-microbiome have also been linked to psychiatric diseases via the gut-brain axis. Not surprisingly, depression and anxiety are often reported in patients with IBD. Dr. Li-Ping Zhao and colleagues looked into the central and peripheral kynurenine pathway (KP) alterations in a mouse... read more

It is becoming appreciated that the kynurenine pathway (KP) plays a role in the pathophysiology and/or progression of numerous neurological diseases. In June 2022 we highlighted a study that demonstrated that KP metabolites may serve as biomarkers of disease progression in Alzheimer’s patients (M. Cespedes et al., 2022). As such, observed KP alterations in Alzheimer’s disease (AD) may serve as a potential therapeutic target. Dr. Dan Cheng and colleagues published a study on how minocycline affected neuroinflammation and the KP in Brain Behavior and Immunity. The chronic unpredictable mild stress (CUMS) model was used in this study to induce a... read more