scholarly journals Role of Kynurenine Pathway in Oxidative Stress during Neurodegenerative Disorders

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1603
Author(s):  
Adrian Mor ◽  
Anna Tankiewicz-Kwedlo ◽  
Anna Krupa ◽  
Dariusz Pawlak
Keyword(s):  
Oxidative Stress ◽  
Neurodegenerative Disorders ◽  
Kynurenine Pathway ◽  
Mitochondrial Damage ◽  
Oxidative Metabolites ◽  
Oxidative Stress Level ◽  
Life Threatening ◽  
Proinflammatory Factors

Neurodegenerative disorders are chronic and life-threatening conditions negatively affecting the quality of patients’ lives. They often have a genetic background, but oxidative stress and mitochondrial damage seem to be at least partly responsible for their development. Recent reports indicate that the activation of the kynurenine pathway (KP), caused by an activation of proinflammatory factors accompanying neurodegenerative processes, leads to the accumulation of its neuroactive and pro-oxidative metabolites. This leads to an increase in the oxidative stress level, which increases mitochondrial damage, and disrupts the cellular energy metabolism. This significantly reduces viability and impairs the proper functioning of central nervous system cells and may aggravate symptoms of many psychiatric and neurodegenerative disorders. This suggests that the modulation of KP activity could be effective in alleviating these symptoms. Numerous reports indicate that tryptophan supplementation, inhibition of KP enzymes, and administration or analogs of KP metabolites show promising results in the management of neurodegenerative disorders in animal models. This review gathers and systematizes the knowledge concerning the role of metabolites and enzymes of the KP in the development of oxidative damage within brain cells during neurodegenerative disorders and potential strategies that could reduce the severity of this process.

Resveratrol: A new potential therapeutic agent for melanoma?

2019 ◽  
Vol 26 ◽  
Author(s):  
Mohamad Hossein Pourhanifeh ◽  
Kazem Abbaszadeh-Goudarzi ◽  
Mohammad Goodarzi ◽  
Sara G.M. Piccirillo ◽  
Alimohammad Shafiee ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Therapeutic Agent ◽  
Current Knowledge ◽  
Treatment Resistance ◽  
Anti Cancer ◽  
Apoptosis Inducer ◽  
Life Threatening ◽  
First Time

: Melanoma is the most life-threatening and aggressive class of skin malignancies. The incidence of melanoma has steadily increased. Metastatic melanoma is greatly resistant to standard anti-melanomatreatments such as chemotherapy, and 5-year survival rate of cases with melanoma who have metastatic form of disease is less than 10%. The contributing role of apoptosis, angiogenesis and autophagy in the pathophysiology of melanoma has been previously demonstrated. Thus, it is extremely urgent to search for complementary therapeutic approachesthat couldenhance the quality of life of subjects and reduce treatment resistance and adverse effects. Resveratrol, known as a polyphenol component present in grapes and some plants, has anti-cancer properties due to its function as an apoptosis inducer in tumor cells, and anti-angiogenic agent to prevent metastasis. However, more clinical trials should be conducted to prove resveratrol efficacy. : Herein, for first time, we summarize current knowledge of anti-cancerous activities of resveratrol in melanoma.

scholarly journals Benefits under the Sea: The Role of Marine Compounds in Neurodegenerative Disorders

Marine Drugs ◽  
2021 ◽  
Vol 19 (1) ◽  
pp. 24
Author(s):  
Mariano Catanesi ◽  
Giulia Caioni ◽  
Vanessa Castelli ◽  
Elisabetta Benedetti ◽  
Michele d’Angelo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Neurodegenerative Disorders ◽  
Extreme Temperature ◽  
Bioactive Molecules ◽  
Neuroprotective Effects ◽  
Physical Conditions ◽  
Adjuvant Therapies ◽  
Marine Habitats ◽  
Marine Compounds

Marine habitats offer a rich reservoir of new bioactive compounds with great pharmaceutical potential; the variety of these molecules is unique, and its production is favored by the chemical and physical conditions of the sea. It is known that marine organisms can synthesize bioactive molecules to survive from atypical environmental conditions, such as oxidative stress, photodynamic damage, and extreme temperature. Recent evidence proposed a beneficial role of these compounds for human health. In particular, xanthines, bryostatin, and 11-dehydrosinulariolide displayed encouraging neuroprotective effects in neurodegenerative disorders. This review will focus on the most promising marine drugs’ neuroprotective potential for neurodegenerative disorders, such as Parkinson’s and Alzheimer’s diseases. We will describe these marine compounds’ potential as adjuvant therapies for neurodegenerative diseases, based on their antioxidant, anti-inflammatory, and anti-apoptotic properties.

scholarly journals Therapy for myeloproliferative neoplasms: when, which agent, and how?

Hematology ◽  
2014 ◽  
Vol 2014 (1) ◽  
pp. 277-286 ◽  
Author(s):  
Holly L. Geyer ◽  
Ruben A. Mesa
Keyword(s):  
Quality Of Life ◽  
Disease Burden ◽  
Myeloproliferative Neoplasms ◽  
Jak Inhibitors ◽  
Symptom Profiles ◽  
Risk Of Progression ◽  
Life Threatening ◽  
Jak2 Inhibition

Abstract Myeloproliferative neoplasms, including polycythemia vera (PV), essential thrombocythemia, and myelofibrosis (MF) (both primary and secondary), are recognized for their burdensome symptom profiles, life-threatening complications, and risk of progression to acute leukemia. Recent advancements in our ability to diagnose and prognosticate these clonal malignancies have paralleled the development of MPN-targeted therapies that have had a significant impact on disease burden and quality of life. Ruxolitinib has shown success in alleviating the symptomatic burden, reducing splenomegaly and improving quality of life in patients with MF. The role and clinical expectations of JAK2 inhibition continues to expand to a variety of investigational arenas. Clinical trials for patients with MF focus on new JAK inhibitors with potentially less myelosuppression (pacritinib) or even activity for anemia (momelotinib). Further efforts focus on combination trials (including a JAK inhibitor base) or targeting new pathways (ie, telomerase). Similarly, therapy for PV continues to evolve with phase 3 trials investigating optimal frontline therapy (hydroxyurea or IFN) and second-line therapy for hydroxyurea-refractory or intolerant PV with JAK inhibitors. In this chapter, we review the evolving data and role of JAK inhibition (alone or in combination) in the management of patients with MPNs.

Role of Polyherbal Formulations of Medicinal Plants From Himalayan Regions in the Management of Diabetes

2022 ◽  
pp. 212-229
Author(s):  
Ashfaq Ahmad Shah ◽  
Sumaira Qayoom ◽  
Amit Gupta ◽  
Aqueel Ur Rehman
Keyword(s):  
Quality Of Life ◽  
Oxidative Stress ◽  
Metabolic Diseases ◽  
Polyphenolic Compounds ◽  
Health Concern ◽  
Glucose Measurement ◽  
Diabetes Research ◽  
Cardiovascular Disorders

Current research on phytochemicals is mainly focused on novel phenolic and polyphenolic compounds expressing their potential as therapeutic agents in various diseases like cancer, autoimmune diseases, cardiovascular disorders, diabetes, oxidative stress-related diseases, as well as their properties to inhibit the growth and proliferation of infectious agents. Among the human physiological disorders, one of the most severe endocrine metabolic diseases is Diabetes mellitus which is a clinical disease distinguished by a deficit in the production of insulin or resistance to the action of insulin. Globally, diabetes is an increasing health concern which is now emerging as an epidemic. About 700-800 plants are exhibiting anti-diabetic activity that has been studied. As far as nanotechnology in diabetes research is concerned, it has made possible the buildout of novel glucose measurement as well as insulin delivery modalities that possess the potential to excellently enhance the quality of life of the diabetic patient.

scholarly journals Circulating Leukocytes and Oxidative Stress in Cardiovascular Diseases: A State of the Art

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Speranza Rubattu ◽  
Maurizio Forte ◽  
Salvatore Raffa
Keyword(s):  
Oxidative Stress ◽  
Cardiovascular Diseases ◽  
Stress Level ◽  
Mononuclear Cells ◽  
Pathological Condition ◽  
Clinical Manifestations ◽  
Therapeutic Interventions ◽  
Oxidative Stress Level ◽  
The Impact

Increased oxidative stress from both mitochondrial and cytosolic sources contributes to the development and the progression of cardiovascular diseases (CVDs), and it is a target of therapeutic interventions. The numerous efforts made over the last decades in order to develop tools able to monitor the oxidative stress level in patients affected by CVDs rely on the need to gain information on the disease state. However, this goal has not been satisfactorily accomplished until now. Among others, the isolation of circulating leukocytes to measure their oxidant level offers a valid, noninvasive challenge that has been tested in few pathological contexts, including hypertension, atherosclerosis and its clinical manifestations, and heart failure. Since leukocytes circulate in the blood stream, it is expected that they might reflect quite closely both systemic and cardiovascular oxidative stress and provide useful information on the pathological condition. The results of the studies discussed in the present review article are promising. They highlight the importance of measuring oxidative stress level in circulating mononuclear cells in different CVDs with a consistent correlation between degree of oxidative stress and severity of CVD and of its complications. Importantly, they also point to a double role of leukocytes, both as a marker of disease condition and as a direct contributor to disease progression. Finally, they show that the oxidative stress level of leukocytes reflects the impact of therapeutic interventions. It is likely that the isolation of leukocytes and the measurement of oxidative stress, once adequately developed, may represent an eligible tool for both research and clinical purposes to monitor the role of oxidative stress on the promotion and progression of CVDs, as well as the impact of therapies.

scholarly journals Neuroinflammation and cognition across psychiatric conditions

CNS Spectrums ◽  
2019 ◽  
Vol 24 (1) ◽  
pp. 4-15 ◽  
Author(s):  
Célia Fourrier ◽  
Gaurav Singhal ◽  
Bernhard T. Baune
Keyword(s):  
Psychiatric Disorders ◽  
Cognitive Impairments ◽  
Kynurenine Pathway ◽  
Homeostatic Plasticity ◽  
Cytokine Levels ◽  
Inflammatory Processes ◽  
Psychiatric Conditions ◽  
First Time

Cognitive impairments reported across psychiatric conditions (ie, major depressive disorder, bipolar disorder, schizophrenia, and posttraumatic stress disorder) strongly impair the quality of life of patients and the recovery of those conditions. There is therefore a great need for consideration for cognitive dysfunction in the management of psychiatric disorders. The redundant pattern of cognitive impairments across such conditions suggests possible shared mechanisms potentially leading to their development. Here, we review for the first time the possible role of inflammation in cognitive dysfunctions across psychiatric disorders. Raised inflammatory processes (microglia activation and elevated cytokine levels) across diagnoses could therefore disrupt neurobiological mechanisms regulating cognition, including Hebbian and homeostatic plasticity, neurogenesis, neurotrophic factor, the HPA axis, and the kynurenine pathway. This redundant association between elevated inflammation and cognitive alterations across psychiatric disorders hence suggests that a cross-disorder approach using pharmacological and nonpharmacological (ie, physical activity and nutrition) anti-inflammatory/immunomodulatory strategies should be considered in the management of cognition in psychiatry.

scholarly journals Endotoxin-Induced Tryptophan Degradation along the Kynurenine Pathway: The Role of Indolamine 2,3-Dioxygenase and Aryl Hydrocarbon Receptor-Mediated Immunosuppressive Effects in Endotoxin Tolerance and Cancer and Its Implications for Immunoparalysis

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Elisa Wirthgen ◽  
Andreas Hoeflich
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Immune Escape ◽  
Endotoxin Tolerance ◽  
Kynurenine Pathway ◽  
Aryl Hydrocarbon ◽  
Tryptophan Degradation ◽  
Inflammatory Stimuli ◽  
Life Threatening ◽  
The Impact

The degradation of tryptophan (TRP) along the kynurenine pathway plays a crucial role as a neuro- and immunomodulatory mechanism in response to inflammatory stimuli, such as lipopolysaccharides (LPS). In endotoxemia or sepsis, an enhanced activation of the rate-limiting enzyme indoleamine 2,3-dioxygenase (IDO) is associated with a higher mortality risk. It is assumed that IDO induced immunosuppressive effects provoke the development of a protracted compensatory hypoinflammatory phase up to a complete paralysis of the immune system, which is characterized by an endotoxin tolerance. However, the role of IDO activation in the development of life-threatening immunoparalysis is still poorly understood. Recent reports described the impact of inflammatory IDO activation and aryl hydrocarbon receptor- (AhR-) mediated pathways on the development of LPS tolerance and immune escape of cancer cells. These immunosuppressive mechanisms offer new insights for a better understanding of the development of cellular dysfunctions in immunoparalysis. This review provides a comprehensive update of significant biological functions of TRP metabolites along the kynurenine pathway and the complex regulation of LPS-induced IDO activation. In addition, the review focuses on the role of IDO-AhR-mediated immunosuppressive pathways in endotoxin tolerance and carcinogenesis revealing the significance of enhanced IDO activity for the establishment of life-threatening immunoparalysis in sepsis.

scholarly journals Applications of Melatonin in Female Reproduction in the Context of Oxidative Stress

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Yonghui Jiang ◽  
Huangcong Shi ◽  
Yue Liu ◽  
Shigang Zhao ◽  
Han Zhao
Keyword(s):  
Oxidative Stress ◽  
Polycystic Ovary ◽  
Oocyte Quality ◽  
Early Embryo ◽  
Female Reproduction ◽  
Adverse Conditions ◽  
Wide Range

Oxidative stress has been recognized as one of the causal mediators of female infertility by affecting the oocyte quality and early embryo development. Improving oxidative stress is essential for reproductive health. Melatonin, a self-secreted antioxidant, has a wide range of effects by improving mitochondrial function and reducing the damage of reactive oxygen species (ROS). This minireview illustrates the applications of melatonin in reproduction from four aspects: physiological ovarian aging, vitrification freezing, in vitro maturation (IVM), and oxidative stress homeostasis imbalance associated with polycystic ovary syndrome (PCOS), emphasising the role of melatonin in improving the quality of oocytes in assisted reproduction and other adverse conditions.

scholarly journals The Role of Antioxidants in the Management of Obsessive-Compulsive Disorder

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Fatemeh Baratzadeh ◽  
Sepideh Elyasi ◽  
Amir Hooshang Mohammadpour ◽  
Sofia Salari ◽  
Amirhossein Sahebkar
Keyword(s):  
Oxidative Stress ◽  
Obsessive Compulsive Disorder ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Human Studies ◽  
Large Sample Size ◽  
Antioxidant Treatment ◽  
Obsessive Compulsive ◽  
Compulsive Disorder

Obsessive-compulsive disorder (OCD) is a chronic neuropsychiatric disorder that has a significant effect on the quality of life. The most effective treatment for OCD is the combination of selective serotonin reuptake inhibitors (SSRI) with cognitive behavior therapy (CBT). However, several adverse effects have been linked with this usual pharmacotherapy, and it is unsuccessful in many patients. The exact pathophysiology of OCD is not completely known, though the role of oxidative stress in its pathogenesis has been proposed recently. This review presents an overview of animal and human studies of antioxidant treatment for OCD. The use of antioxidants against oxidative stress is a novel treatment for several neurodegenerative and neuropsychiatric disorders. Among antioxidants, NAC was one of the most studied drugs on OCD, and it showed a significant improvement in OCD symptoms. Thus, antioxidants could be promising as an adjuvant treatment for OCD. However, a limited number of human studies are conducted on these agents, and for better judgment, human studies with a large sample size are necessary.

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