Oxidative Stress and Rare Diseases: From Molecular Crossroads to Therapeutic Avenues

Carlos Romá-Mateo; José Luis García-Giménez

doi:10.3390/antiox10040617

Oxidative Stress, a Crossroad Between Rare Diseases and Neurodegeneration

Antioxidants ◽

10.3390/antiox9040313 ◽

2020 ◽

Vol 9 (4) ◽

pp. 313 ◽

Cited By ~ 4

Author(s):

Carmen Espinós ◽

Máximo Ibo Galindo ◽

María Adelaida García-Gimeno ◽

José Santiago Ibáñez-Cabellos ◽

Dolores Martínez-Rubio ◽

...

Keyword(s):

Oxidative Stress ◽

Rare Diseases ◽

Reactive Nitrogen Species ◽

Neuromuscular Disorders ◽

Common Factor ◽

Drug Resistant ◽

Brain Iron ◽

Pediatric Drug ◽

Inherited Retinal Dystrophies ◽

Retinal Dystrophies

: Oxidative stress is an imbalance between production and accumulation of oxygen reactive species and/or reactive nitrogen species in cells and tissues, and the capacity of detoxifying these products, using enzymatic and non-enzymatic components, such as glutathione. Oxidative stress plays roles in several pathological processes in the nervous system, such as neurotoxicity, neuroinflammation, ischemic stroke, and neurodegeneration. The concepts of oxidative stress and rare diseases were formulated in the eighties, and since then, the link between them has not stopped growing. The present review aims to expand knowledge in the pathological processes associated with oxidative stress underlying some groups of rare diseases: Friedreich’s ataxia, diseases with neurodegeneration with brain iron accumulation, Charcot-Marie-Tooth as an example of rare neuromuscular disorders, inherited retinal dystrophies, progressive myoclonus epilepsies, and pediatric drug-resistant epilepsies. Despite the discrimination between cause and effect may not be easy on many occasions, all these conditions are Mendelian rare diseases that share oxidative stress as a common factor, and this may represent a potential target for therapies.

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Lycopene alleviates sulfamethoxazole-induced hepatotoxicity in grass carp (Ctenopharyngodon idellus) via suppression of oxidative stress, inflammation and apoptosis

Food & Function ◽

10.1039/d0fo01638a ◽

2020 ◽

Vol 11 (10) ◽

pp. 8547-8559

Author(s):

Hongjing Zhao ◽

Yu Wang ◽

Mengyao Mu ◽

Menghao Guo ◽

Hongxian Yu ◽

...

Keyword(s):

Oxidative Stress ◽

Secondary Metabolites ◽

Human Health ◽

Grass Carp ◽

Aquatic Environment ◽

Ctenopharyngodon Idellus

Antibiotics are used worldwide to treat diseases in humans and other animals; most of them and their secondary metabolites are discharged into the aquatic environment, posing a serious threat to human health.

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Copper-dependent ATP7B up-regulation drives the resistance of TMEM16A-overexpressing head-and-neck cancer models to platinum toxicity

Biochemical Journal ◽

10.1042/bcj20190591 ◽

2019 ◽

Vol 476 (24) ◽

pp. 3705-3719 ◽

Cited By ~ 2

Author(s):

Avani Vyas ◽

Umamaheswar Duvvuri ◽

Kirill Kiselyov

Keyword(s):

Oxidative Stress ◽

Head And Neck ◽

Transcriptional Activation ◽

Platinum Resistance ◽

Mrna Levels ◽

Strong Positive Correlation ◽

Platinum Compounds ◽

Copper Chelation ◽

Novel Approach ◽

Cancer Models

Platinum-containing drugs such as cisplatin and carboplatin are routinely used for the treatment of many solid tumors including squamous cell carcinoma of the head and neck (SCCHN). However, SCCHN resistance to platinum compounds is well documented. The resistance to platinum has been linked to the activity of divalent transporter ATP7B, which pumps platinum from the cytoplasm into lysosomes, decreasing its concentration in the cytoplasm. Several cancer models show increased expression of ATP7B; however, the reason for such an increase is not known. Here we show a strong positive correlation between mRNA levels of TMEM16A and ATP7B in human SCCHN tumors. TMEM16A overexpression and depletion in SCCHN cell lines caused parallel changes in the ATP7B mRNA levels. The ATP7B increase in TMEM16A-overexpressing cells was reversed by suppression of NADPH oxidase 2 (NOX2), by the antioxidant N-Acetyl-Cysteine (NAC) and by copper chelation using cuprizone and bathocuproine sulphonate (BCS). Pretreatment with either chelator significantly increased cisplatin's sensitivity, particularly in the context of TMEM16A overexpression. We propose that increased oxidative stress in TMEM16A-overexpressing cells liberates the chelated copper in the cytoplasm, leading to the transcriptional activation of ATP7B expression. This, in turn, decreases the efficacy of platinum compounds by promoting their vesicular sequestration. We think that such a new explanation of the mechanism of SCCHN tumors’ platinum resistance identifies novel approach to treating these tumors.

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Clinical aspects of reactive oxygen and nitrogen species

Biochemical Society Symposium ◽

10.1042/bss0710121 ◽

2004 ◽

Vol 71 ◽

pp. 121-133 ◽

Cited By ~ 25

Author(s):

Ascan Warnholtz ◽

Maria Wendt ◽

Michael August ◽

Thomas Münzel

Keyword(s):

Oxidative Stress ◽

Reactive Oxygen Species ◽

Risk Factor ◽

Endothelial Dysfunction ◽

Vascular Tissue ◽

Rapid Development ◽

Reactive Oxygen ◽

Clinical Aspects ◽

No Production ◽

Oxygen Species

Endothelial dysfunction in the setting of cardiovascular risk factors, such as hypercholesterolaemia, hypertension, diabetes mellitus and chronic smoking, as well as in the setting of heart failure, has been shown to be at least partly dependent on the production of reactive oxygen species in endothelial and/or smooth muscle cells and the adventitia, and the subsequent decrease in vascular bioavailability of NO. Superoxide-producing enzymes involved in increased oxidative stress within vascular tissue include NAD(P)H-oxidase, xanthine oxidase and endothelial nitric oxide synthase in an uncoupled state. Recent studies indicate that endothelial dysfunction of peripheral and coronary resistance and conductance vessels represents a strong and independent risk factor for future cardiovascular events. Ways to reduce endothelial dysfunction include risk-factor modification and treatment with substances that have been shown to reduce oxidative stress and, simultaneously, to stimulate endothelial NO production, such as inhibitors of angiotensin-converting enzyme or the statins. In contrast, in conditions where increased production of reactive oxygen species, such as superoxide, in vascular tissue is established, treatment with NO, e.g. via administration of nitroglycerin, results in a rapid development of endothelial dysfunction, which may worsen the prognosis in patients with established coronary artery disease.

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The Collaborative Network Approach: a model for advancing patient-centric research for Castleman disease and other rare diseases

Emerging Topics in Life Sciences ◽

10.1042/etls20180178 ◽

2019 ◽

Vol 3 (1) ◽

pp. 97-105

Author(s):

Mary Zuccato ◽

Dustin Shilling ◽

David C. Fajgenbaum

Keyword(s):

Rare Diseases ◽

Treatment Options ◽

Castleman Disease ◽

High Impact ◽

Collaborative Network ◽

Network Approach ◽

Grant Applications ◽

Research Questions ◽

Novel Strategy ◽

Patient Centric

Abstract There are ∼7000 rare diseases affecting 30 000 000 individuals in the U.S.A. 95% of these rare diseases do not have a single Food and Drug Administration-approved therapy. Relatively, limited progress has been made to develop new or repurpose existing therapies for these disorders, in part because traditional funding models are not as effective when applied to rare diseases. Due to the suboptimal research infrastructure and treatment options for Castleman disease, the Castleman Disease Collaborative Network (CDCN), founded in 2012, spearheaded a novel strategy for advancing biomedical research, the ‘Collaborative Network Approach’. At its heart, the Collaborative Network Approach leverages and integrates the entire community of stakeholders — patients, physicians and researchers — to identify and prioritize high-impact research questions. It then recruits the most qualified researchers to conduct these studies. In parallel, patients are empowered to fight back by supporting research through fundraising and providing their biospecimens and clinical data. This approach democratizes research, allowing the entire community to identify the most clinically relevant and pressing questions; any idea can be translated into a study rather than limiting research to the ideas proposed by researchers in grant applications. Preliminary results from the CDCN and other organizations that have followed its Collaborative Network Approach suggest that this model is generalizable across rare diseases.

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