Asthma is caused by or worsened by different things in different people. It is because of these differences that not all people with asthma respond the same to all treatments and medicines. If the investigators can better identify the changes in the airways or breathing pipes in patients with asthma, the investigators may be able to help patients make better choices about the medicines or treatments that are most likely to work best for each patient.
This research study is about one specific factor that is known to affect asthma in some patients. It involves an increase in the activity of an enzyme that is in people's airways. An enzyme is something that helps a chemical reaction to occur. The enzyme the investigators are studying in this research study is called GSNOR (S-nitrosoglutathione reductase) , and when the activity of this enzyme is increased, the result is that there is less GSNO (S-nitrosoglutathione) . GSNO is a chemical that protects people's airways. The initials stand for S-nitrosoglutathione, (pronounced s-nahy-troh-soh-gloo-tuh-thahy-ohn), and it is naturally produced by the body. It has an important role in regulating respiratory function (breathing) and preventing inflammation (swelling) in the respiratory tract (throat, airways, and lungs).
The amount of GSNO found in the body is controlled by the enzyme GSNOR (S-nitrosoglutathione reductase). GSNOR breaks down GSNO. Too much GSNOR leads to low levels of GSNO, and that can cause inflammation (swelling) and loss of airway function in some asthma patients.
The only way to measure GSNOR levels currently is with a bronchoscopy procedure where a scope is inserted into the patient's airways, often under sedation. This research study is being done to test the accuracy of another type of test that can be done in the doctor's office, rather than in a procedure area. This non-invasive diagnostic test, called a GSNO Challenge test, may be able to identify which asthma patients have increased activity of the airway enzyme GSNOR. The investigators are also studying the phenotypes (observable traits) in asthma patients with increased levels of GSNOR. If this research study is successful, in the future (after this research study is done). The investigators may be able to offer a cost-effective and non-invasive way to identify patients who have higher GSNOR activity levels and offer personalized treatments.
The GSNO Challenge test includes giving an investigational drug to breathe in (inhale). The investigational drug is GSNO. "Investigational" means the drug is not approved by any regulatory agencies including the Food and Drug Administration (FDA), and is still being tested for safety and effectiveness. The research is registered with the FDA, but again the GSNO treatment in this study (administered during the GSNO challenge testing) is not an approved treatment or diagnostic test for asthma.

Start Date30 Apr 2019

Sponsor / Collaborator

Case Western Reserve University

[+3]

100 Clinical Results associated with S-Nitrosoglutathione

100 Translational Medicine associated with S-Nitrosoglutathione

100 Patents (Medical) associated with S-Nitrosoglutathione

1,172

Literatures (Medical) associated with S-Nitrosoglutathione

01 Jan 2025·Food Chemistry

Fabrication and application of gold nanoparticles functionalized polymer monolith in spin column for the determination of S-nitrosoglutathione in meat

Article

Author: Lv, Xiaoyuan ; Wang, Xin ; Zhang, Shengman ; Zhou, Wenxiu ; Li, Bingjie

S-nitrosoglutathione (GSNO) is the most important S-nitrosothiol in vivo, which could affect the quality of meat by participating in calcium release, glucose metabolism, proteolysis and apoptosis, therefore may potentially serve as a marker for meat freshness. In this work, a solid-phase extraction (SPE) monolithic spin column modified with gold nanoparticles was prepared for GSNO extraction. The optimized SPE-LC-MS/MS method for GSNO quantification displays low limit of detection (0.01 nM), good precision (RSD < 15 %) and acceptable recovery (> 77.7 %). Furthermore, this approach has been applied to monitor GSNO levels in beef and pork stored at -20 °C for different days, showing that endogenous GSNO level increases during prolonged storage and could be employed as a marker to evaluate the freshness of ice stored meat. Additionally, the monolithic spin column remains in good quality after a half-year storage, which is promising to develop into commercial enrichment kit for endogenous GSNO analysis.

01 Dec 2024·Cellular Signalling

S-nitrosoglutathione (GSNO) induces necroptotic cell death in K562 cells: Involvement of p73, TSC2 and SIRT1

Article

Author: Biswas, Sanchita ; Sengupta, Ayantika ; Ghosh, Sanjay ; Patra, Sourav Kumar ; Chakraborty, Subhamoy

BACKGROUNDNitric oxide and Reactive Nitrogen Species are known to effect tumorigenicity. GSNO is one of the main NO carrying signalling moiety in cell. In the current study, we tried to delve into the effect of GSNO induced nitrosative stress in three different myelogenous leukemic K562, U937 and THP-1 cell lines.METHODWST-8 assay was performed to investigate cell viability. RT-PCR and western-blot analysis were done to investigate mRNA and protein expression. Spectrophotometric and fluorimetric assays were done to investigate enzyme activities.RESULTWe found that GSNO exposure led to reduced cell viability and the mode of cell death in K562 was non apoptotic in nature. GSNO promoted impaired autophagic flux and necroptosis. GSNO treatment heightened phosphorylation of AMPK and TSC2 and inhibited mTOR pathway. We observed increase in NAD⁺/ NADH ratio following GSNO treatment. Increase in both SIRT1 m-RNA and protein expression was observed. While total SIRT activity remained unaltered. GSNO increased tumor suppressor TAp73/ oncogenic ∆Np73 ratio in K562 cells which was correlated with cell mortality. Surprisingly, GSNO did not alter cellular redox status or redox associated protein expression. However, steep increase in total SNO and PSNO content was observed. Furthermore, inhibition of autophagy, AMPK phosphorylation or SIRT1 exacerbated the effect of GSNO. Altogether our work gives insights into GSNO mediated necroptotic event in K562 cells which can be excavated to develop NO based anticancer therapeutics.CONCLUSIONOur data suggests that GSNO could induce necroptotic cell death in K562 through mitochondrial dysfunctionality and PTM of different cellular proteins.

01 Nov 2024·Free Radical Biology and Medicine

Systematic analysis of the global characteristics and reciprocal effects of S-nitrosylation and S-persulfidation in the human proteome

Article

Author: Yang, Jing ; Huang, Yaqian ; Jin, Hongfang ; Tang, Chaoshu ; Fu, Ling ; Li, Zongmin ; Du, Junbao ; Peng, Hanlin ; Lv, Boyang

Gasotransmitter-mediated cysteine post-translational modifications, including S-nitrosylation (SNO) and S-persulfidation (SSH), play crucial roles and interact in various biological processes. However, there has been a delay in appreciating the interactional rules between SNO and SSH. Here, all human S-nitrosylated and S-persulfidated proteomic data were curated, and comprehensive analyses from multiple perspectives, including sequence, structure, function, and exact protein impacts (e.g., up-/down-regulation), were performed. Although these two modifications collectively regulated a wide array of proteins to jointly maintain redox homeostasis, they also exhibited intriguing differences. First, SNO tended to be more accessible and functionally clustered in pathways associated with cell damage repair and other protein modifications, such as phosphorylation and ubiquitination. Second, SSH preferentially targeted cysteines in disulfide bonds and modulated tissue development and immune-related pathways. Finally, regardless of whether SNO and SSH occupied the same position of a given protein, their combined effect tended to be suppressive when acting synergistically; otherwise, SNO likely inhibited while SSH activated the target protein. Indeed, a side-by-side comparison of SNO and SSH shed light on their globally reciprocal effects and provided a reference for further research on gasotransmitter-mediated biological effects.

News (Medical) associated with S-Nitrosoglutathione

20 Oct 2022

·www.biospace.com

AlzeCure Presents New Data with its Preventive Treatment Alzstatin at the Alzheimer Conference CTAD

STOCKHOLM, SWEDEN / ACCESSWIRE / October 20, 2022 / AlzeCure Pharma (STO:ALZCUR)(FRA:AC6) AlzeCure Pharma AB (publ) (FN STO:ALZCUR), a pharmaceutical company that develops a broad portfolio of small molecule drug candidates for diseases affecting the central nervous system, with projects in both Alzheimer's disease and pain, today announced that an abstract with new preclinical Alzstatin data has been accepted for presentation at the annual Alzheimer conference CTAD, Clinical Trials in Alzheimer's Disease, which this year is being held in San Francisco on November 29 - December 2. The abstract, titled AC-0027875, a novel gamma-secretase modulator for the treatment of Alzheimer's disease, will be presented at the international Alzheimer conference CTAD 2022 by Dr. Johan Sandin, CSO at AlzeCure. The other co-authors are Dr. Märta Dahlström, Dr. Maria Backlund, Veronica Lidell, Azita Rasti, Sanja Juric, Dr. Magnus Halldin, Director of Discovery DMPK & Safety assessment at AlzeCure, Dr. Pontus Forsell, Head of Discovery & Research at AlzeCure, and Dr. Gunnar Nordvall, Director of Medicinal Chemistry at AlzeCure. The presentation includes new preclinical results with AlzeCure's compound AC-0027875, which is a new potent small molecule gamma-secretase modulator (GSM) and part of AlzeCure's research platform Alzstatin®. The substance exhibits potent effects on the production of toxic Aβ42 and reduces levels by over 50% in vivo. GSM's represents a promising class of Aβ42-lowering anti-amyloidogenic substances for the treatment of Alzheimer's disease. It exhibits several key properties that makes it suitable as a preventive or disease-modifying treatment for Alzheimer's disease. "AC-0027875 rapidly reaches the brain in relevant concentrations and greatly reduces the amount of toxic Aβ42. The mechanism of Alzstatin lends itself particularly well to early, preventive treatment, and these promising data demonstrate the potent effects of our substances," said Johan Sandin, CSO at AlzeCure Pharma. "The goal of Alzstatin is to be able to offer a preventive and disease-modifying treatment against Alzheimer's in tablet form, and with these new data and the increased interest in the field, I look positively on the continued development work and outlicensing discussions," said Martin Jönsson, CEO of AlzeCure Pharma. The abstract and poster will be available on AlzeCure's website after the presentation ( ). For more information, please contact Martin Jönsson, CEO Tel: +46 707 86 94 43 martin.jonsson@alzecurepharma.com About AlzeCure Pharma AB (publ) AlzeCure® is a Swedish pharmaceutical company that develops new innovative small molecule drug therapies for the treatment of severe diseases and conditions that affect the central nervous system, such as Alzheimer's disease and pain - indications for which currently available treatment is very limited. The company is listed on Nasdaq First North Premier Growth Market and is developing several parallel drug candidates based on three research platforms: NeuroRestore®, Alzstatin® and Painless. NeuroRestore consists of two symptomatic drug candidates where the unique mechanism of action allows for multiple indications, including Alzheimer's disease, as well as cognitive disorders associated with traumatic brain injury, sleep apnea and Parkinson's disease. The Alzstatin platform focuses on developing disease-modifying and preventive drug candidates for early treatment of Alzheimer's disease and comprises two drug candidates. Painless is the company's research platform in the field of pain and contains two projects: ACD440, which is a drug candidate in the clinical development phase for the treatment of neuropathic pain, and TrkA-NAM, which targets other types of severe pain in conditions such as osteoarthritis. AlzeCure aims to pursue its own projects through preclinical research and development through an early clinical phase and is continually working on business development to find suitable solutions for license agreements with other pharmaceutical companies. FNCA Sweden AB is the company's Certified Adviser. For more information, please visit About Alzstatin® AlzeCure's disease-modifying research platform, Alzstatin, consisting of disease-modifying and preventive drug candidates, focuses on reducing the production of toxic amyloid beta (Aβ), such as Aβ42, in the brain. Aβ42 plays a key pathological role in Alzheimer's and begins to accumulate in the brain years before clear symptoms develop. The drug candidates in the Alzstatin platform modulate the function of the enzyme gamma secretase. Gamma secretase acts like a pair of scissors and cuts Aβ42 out from a longer protein known as APP. The sticky Aβ42 clumps together giving rise to the amyloid plaque so typical of Alzheimer's disease. The candidates in the Alzstatin platform affect enzyme function so that it instead cuts out shorter forms of the Aβ peptide, Aβ37 and Aβ38, which in addition to them not being sticky and not forming aggregates, also have a restrictive effects on Aβ42 aggregates already formed. This means the drug candidates in the Alzstatin platform have two separate but synergistic effects that together contribute to a stronger anti-amyloidogenic - and thus more potent - disease-modifying effect. This specific mechanism of action differentiates it from biological therapies, e.g. antibodies. Moreover, small molecules such as Alzstatin, have several other advantages, including easy and non-invasive administration as tablets or capsules. Small molecules will also generally pass more readily through the blood-brain barrier to reach its target, the brain. Image Attachments Martin Jönsson CEO And Johan Sandin CSO AlzeCure Pharma Attachments AlzeCure presents new data with its preventive treatment Alzstatin at the Alzheimer conference CTAD SOURCE: AlzeCure Pharma View source version on accesswire.com:

AntibodySmall molecular drug

100 Deals associated with S-Nitrosoglutathione

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Asthma	Phase 3	US	Nivalis Therapeutics, Inc.	-
Cystic Fibrosis	Phase 3	-	NitroMed, Inc.	-
Cystic Fibrosis	Phase 3	US	Nivalis Therapeutics, Inc.	-
Pulmonary Disease, Chronic Obstructive	Phase 3	US	Nivalis Therapeutics, Inc.	-
Pulmonary Disease, Chronic Obstructive	Phase 3	-	NitroMed, Inc.	-
Alzheimer Disease	Preclinical	IN	University of Delhi	14 May 2024
Alzheimer Disease	Preclinical	US	Michigan State University	14 May 2024
Asthma	Discovery	-	NitroMed, Inc.	-

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