Inflammation Marker 7 ,8-Dihydroneopterin Induces Apoptosis of Neurons and Glial Cells: a Potential Contribution to Neurodegenerative Processes

Speth, Cornelia; Stöckl, Gabriele; Fuchs, Dietmar; Wirleitner, Barbara; Widner, Bernhard; Würzner, Reinhard; Mohsenipour, Iradji; Lass‐Flörl, Cornelia; Dierich, Manfred P.

doi:10.1016/s0171-2985(00)80104-7

Cited by 19 publications

(11 citation statements)

References 29 publications

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“…In various diseases with neurological complications, such as multiple sclerosis and HIV infection with the AIDS dementia complex, elevated neopterin levels have been found in cerebrospinal fluid [31,32]. The source of neopterin in cerebrospinal fluid in these diseases remains unclear, but an in vitro study has suggested that neopterin in the brain might derive from infiltrating macrophages and monocytes, since astrocytes, microglia and neurons were not able to produce neopterin [33]. The same study also showed that neopterin itself had no effect on the viability of brain cells, but its derivative 7,8-dihydroneopterin was able to induce apoptosis in astrocytes and neurons in a dose-dependent manner [33].…”

Section: Discussionmentioning

confidence: 99%

“…The source of neopterin in cerebrospinal fluid in these diseases remains unclear, but an in vitro study has suggested that neopterin in the brain might derive from infiltrating macrophages and monocytes, since astrocytes, microglia and neurons were not able to produce neopterin [33]. The same study also showed that neopterin itself had no effect on the viability of brain cells, but its derivative 7,8-dihydroneopterin was able to induce apoptosis in astrocytes and neurons in a dose-dependent manner [33]. It might be possible that neopterin is associated with delirium through the indirect induction of apoptosis in the brain.…”

Section: Discussionmentioning

confidence: 99%

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Neopterin: A Potential Biomarker for Delirium in Elderly Patients

Egberts¹,

Wijnbeld²,

Fekkes³

et al. 2014

Dement Geriatr Cogn Disord

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Background/Aims: The diagnosis of delirium is not supported by specific biomarkers. In a previous study, high neopterin levels were found in patients with a postoperative delirium. In the present study, we investigated levels of neopterin, interleukin-6 (IL-6) and insulin-like growth factor-1 (IGF-1) in acutely ill admitted elderly patients with and without a delirium. Methods: Plasma/serum levels ofneopterin, IL-6 and IGF-1 were determined in patients aged ≥65 years admitted to the wards of Internal Medicine and Geriatrics. Differences in biomarker levels between patients with and without a delirium were investigated by the analysis of variance in models adjusted for age, gender, comorbidities and eGFR (when appropriate). Results: Eighty-six patients were included; 23 of them with a delirium. In adjusted models, higher mean levels of neopterin (70.5 vs. 45.9 nmol/l, p = 0.009) and IL-6 (43.1 vs. 18.5 pg/ml, p = 0.034) and lower mean levels of IGF-1 (6.3 vs. 9.3 nmol/l, p = 0.007) were found in patients with a delirium compared to those without. Conclusions: The findings of this study suggest that neopterin might be a potential biomarker for delirium which, through oxidative stress and activation of the immune system, may play a role in the pathophysiology of delirium. © 2014 S. Karger AG, Basel

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Neopterin: A Potential Biomarker for Delirium in Elderly Patients

Egberts¹,

Wijnbeld²,

Fekkes³

et al. 2014

Dement Geriatr Cogn Disord

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“…Oxidative stress might be enforced by pro-oxidative effects of neopterin derivatives [95][96][97]. By enhancement of oxidative stress neopterin derivatives are able to accelerate the replication rate of HIV [98,99].…”

Section: Neopterin and Formation Of Reactive Oxygen Speciesmentioning

confidence: 99%

“…Furthermore pteridines also have proapoptotic effects, especially 7, 8-dihydroneopterin has been shown to induce apoptosis e.g. via Fas-L expression in several cells and cell lines [96,97,[101][102][103].…”

Section: Neopterin and Formation Of Reactive Oxygen Speciesmentioning

confidence: 99%

“…Also neopterin is able to penetrate through the blood-brainbarrier [150].The pro-oxidative activities of neopterin derivatives might enhance oxidative stress in the brain and induce apoptosis in neuronal cells [96,97,103]. Elevated neopterin concentrations are found in the CSF of HIV infected patients, and strong intrathecal formation of neopterin has been described in HIV-associated dementia, with CSF neopterin concentrations being much higher than serum values [135,151].…”

Section: Ifn--mediated Pathways and Specific Symp-toms In Hiv Infectimentioning

confidence: 99%

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Indoleamine-2, 3-Dioxygenase and Other Interferon-γ-Mediated Pathways in Patients with Human Immunodeficiency Virus Infection

Schroecksnadel

Zangerle

Bellmann‐Weiler

et al. 2007

CDM

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Human immunodeficiency virus type 1 (HIV) infection is characterized by progressive immunodeficiency despite of an overwhelming cellular immune activation. Patients show highly elevated serum/plasma concentrations of the proinflammatory cytokine interferon-(IFN-), which induces human monocytes to form neopterin, to produce reactive oxygen species (ROS) and in parallel, to degrade tryptophan. Enhanced tryptophan degradation by the enzyme indoleamine-2, 3-dioxygenase (IDO) contributes importantly to disease progression and "complications" of HIV infection: By a subsequent impairment of protein metabolism and serotonin formation, the development of neuropsychiatric disorders and weight loss in HIV infected patients can be enforced. Furthermore, increased IDO-activation efficiently suppresses the growth and proliferation of pathogens as well as host T-cells. IDO and other IFN--mediated pathways are strongly induced in patients with HIV infection and are also linked with disease progression: Neopterin formation by GTPcyclohydrolase I sensitively reflects the stage of the disease, and determination of the pteridine in body fluids is useful to monitor the efficacy of antiretroviral therapy. Neopterin is an independent prognostic factor for the outcome of disease, and well suited to estimate the degree of immune activation in vivo and the responsiveness of immunocompetent cells to stimulation in vitro. ROS formation may contribute to the development of oxidative stress in HIV infection, resulting in depletion of antioxidants. The cause-effective role of an overwhelming Th1-type immune response together with the activation of IDO and other IFN--mediated biochemical pathways for the course of HIV infection, the development of immunodeficiency, anemia and weight loss in HIV patients is discussed.

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Potential role of immune system activation-associated production of neopterin derivatives in humans

Hoffmann

Wirleitner

Fuchs

2003

Inflammation Research

214

152

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Neopterin derivatives are produced by human monocyte-derived macrophages and dendritic cells upon stimulation with interferons. Neopterin concentrations measured in urine or blood reflect activation of cellular immunity and endogenous release of interferon-gamma. This review focuses on the clinical utility of measuring neopterin levels in inflammatory disease and the potential functions of neopterin as a mediator and/or modulator in the course of inflammatory and infectious processes. In vitro-studies revealed that neopterin derivatives exhibit distinct biochemical effects, most likely via interactions with reactive oxygen or nitrogen intermediates, thereby affecting the cellular redox state. Data support the hypothesis that the release of neopterin enhances the cytotoxic potential of activated macrophages and dendritic cells. In vivo, a strong correlation between neopterin levels and the severity, progression, and outcome of infectious and inflammatory diseases was found. The influence of neopterin derivatives on the cellular metabolism may provide an explanation for these clinical observations.

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Inflammation Marker 7 ,8-Dihydroneopterin Induces Apoptosis of Neurons and Glial Cells: a Potential Contribution to Neurodegenerative Processes

Cited by 19 publications

References 29 publications

Neopterin: A Potential Biomarker for Delirium in Elderly Patients

Neopterin: A Potential Biomarker for Delirium in Elderly Patients

Indoleamine-2, 3-Dioxygenase and Other Interferon-γ-Mediated Pathways in Patients with Human Immunodeficiency Virus Infection

Potential role of immune system activation-associated production of neopterin derivatives in humans

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Inflammation Marker 7 ,8-Dihydroneopterin Induces Apoptosis of Neurons and Glial Cells: a Potential Contribution to Neurodegenerative Processes

Cited by 19 publications

References 29 publications

Neopterin: A Potential Biomarker for Delirium in Elderly Patients

Neopterin: A Potential Biomarker for Delirium in Elderly Patients

Indoleamine-2, 3-Dioxygenase and Other Interferon-&#947;-Mediated Pathways in Patients with Human Immunodeficiency Virus Infection

Potential role of immune system activation-associated production of neopterin derivatives in humans

Contact Info

Product

Resources

About

Indoleamine-2, 3-Dioxygenase and Other Interferon-γ-Mediated Pathways in Patients with Human Immunodeficiency Virus Infection