Iron chelation as a potential therapy for neurodegenerative disease

2008 ◽  
Vol 36 (6) ◽  
pp. 1304-1308 ◽  
Author(s):  
Robert C. Hider ◽  
Yongmin Ma ◽  
Francisco Molina-Holgado ◽  
Alessandra Gaeta ◽  
Sourav Roy
Keyword(s):  
Oxidative Stress ◽  
Neurodegenerative Disorders ◽  
Rational Design ◽  
Chelation Therapy ◽  
Iron Chelation ◽  
Therapeutic Agents ◽  
Disease States ◽  
Pathological Conditions ◽  
Pharmacological Targets ◽  
And Oxidative Stress

Neurodegenerative disorders include a variety of pathological conditions, which share similar critical metabolic processes such as protein aggregation and oxidative stress, both of which are associated with the involvement of metal ions. Chelation therapy could provide a valuable therapeutic approach to such disease states, since metals, particularly iron, are realistic pharmacological targets for the rational design of new therapeutic agents.

scholarly journals N-Acetyl-Cysteine supplementation lowers high homocysteine plasma levels and increases Glutathione synthesis in the trans-sulfuration pathway

2019 ◽  
Vol 13 (4) ◽  
pp. 234-240
Author(s):  
Federico Cacciapuoti
Keyword(s):  
Oxidative Stress ◽  
Neurodegenerative Disorders ◽  
Active Form ◽  
The Body ◽  
Glutamate Cysteine Ligase ◽  
Pathological Conditions ◽  
Transsulfuration Pathway ◽  
Antioxidant Function ◽  
Acetyl Cysteine ◽  
Rate Limiting

Glutathione (GSH), a compound derived of a combination of three amino acids – cysteine, glycine and glutamine – is the final product of homocysteine (Hcy) metabolism  in the transsulfuration pathway. The major determinants of GSH synthesis are the availability of cysteine and the activity of the rate-limiting enzyme, glutamate cysteine ligase (GCL). A deficiency in  transsulfuration pathway leads to excessive Hcy production (HHcy) and reduced GSH synthesis. This tripeptide, that exists in the reduced or active  form (GSH) and oxidized variant (GSH), is the main antioxidant of the  body.  Independently of its antioxidant function, the compound  has an anti-inflammatory role too, reducing the production of interleukines and the expression of TNF-alfa and iNOS synthase. A dysregulation of GSH synthesis is recognized as contributing factor to the pathogenesis of many pathological conditions. But, the insufficiency of the transsulfuration pathway is also responsible of HHcy. Besides, this condition  decreases the activity of cellular “gluthatione peroxidase”, an intracellular antioxidant enzyme that reduces hydrogen peroxide to water with the prevalence of GSSH on GSH. The consequent GSH/GSSH impaired ratio also causes some common cardiovascular and neurodegenerative disorders. In both occurrences, N-Acetyl-Cysteine (NAC) supplementation supplies the cysteine necessary for GSH synthesis and contemporarily reduces HHcy, improving  the GPx1 activity and further reducing oxidative stress.

scholarly journals Does the Interdependence between Oxidative Stress and Inflammation Explain the Antioxidant Paradox?

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Subrata Kumar Biswas
Keyword(s):  
Oxidative Stress ◽  
Chronic Diseases ◽  
Inflammatory Process ◽  
The Other ◽  
Present Review ◽  
Low Grade ◽  
Inflammatory Pathways ◽  
Pathological Conditions ◽  
Other Hand ◽  
And Oxidative Stress

Oxidative stress has been implicated in many chronic diseases. However, antioxidant trials are so far largely unsuccessful as a preventive or curative measure. Chronic low-grade inflammatory process, on the other hand, plays a central role in the pathogenesis of a number of chronic diseases. Oxidative stress and inflammation are closely related pathophysiological processes, one of which can be easily induced by another. Thus, both processes are simultaneously found in many pathological conditions. Therefore, the failure of antioxidant trials might result from failure to select appropriate agents that specifically target both inflammation and oxidative stress or failure to use both antioxidants and anti-inflammatory agents simultaneously or use of nonselective agents that block some of the oxidative and/or inflammatory pathways but exaggerate the others. To examine whether the interdependence between oxidative stress and inflammation can explain the antioxidant paradox we discussed in the present review the basic aspects of oxidative stress and inflammation and their relationship and dependence.

scholarly journals Mitochondrial and Organellar Crosstalk in Parkinson’s Disease

ASN NEURO ◽  
2021 ◽  
Vol 13 ◽  
pp. 175909142110283
Author(s):  
Bipul Ray ◽  
Abid Bhat ◽  
Arehally Marappa Mahalakshmi ◽  
Sunanda Tuladhar ◽  
Muhammed Bishir ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mitochondrial Dysfunction ◽  
Protein Misfolding ◽  
Contact Sites ◽  
Physiological Processes ◽  
Pathological Conditions ◽  
And Oxidative Stress ◽  
Pathological Event

Mitochondrial dysfunction is a well-established pathological event in Parkinson’s disease (PD). Proteins misfolding and its impaired cellular clearance due to altered autophagy/mitophagy/pexophagy contribute to PD progression. It has been shown that mitochondria have contact sites with endoplasmic reticulum (ER), peroxisomes and lysosomes that are involved in regulating various physiological processes. In pathological conditions, the crosstalk at the contact sites initiates alterations in intracellular vesicular transport, calcium homeostasis and causes activation of proteases, protein misfolding and impairment of autophagy. Apart from the well-reported molecular changes like mitochondrial dysfunction, impaired autophagy/mitophagy and oxidative stress in PD, here we have summarized the recent scientific reports to provide the mechanistic insights on the altered communications between ER, peroxisomes, and lysosomes at mitochondrial contact sites. Furthermore, the manuscript elaborates on the contributions of mitochondrial contact sites and organelles dysfunction to the pathogenesis of PD and suggests potential therapeutic targets.

scholarly journals Heparanase Inhibition Reduces Glucose Levels, Blood Pressure, and Oxidative Stress in Apolipoprotein E Knockout Mice

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Shadi Hamoud ◽  
Rabia Shekh Muhammad ◽  
Niroz Abu-Saleh ◽  
Ahmad Hassan ◽  
Yaniv Zohar ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Apolipoprotein E ◽  
Serum Glucose ◽  
The Other ◽  
Control Group ◽  
Glucose Levels ◽  
Disease States ◽  
Apolipoprotein E Knockout Mice ◽  
And Oxidative Stress

Background.Atherosclerosis is a multifactorial process. Emerging evidence highlights a role of the enzyme heparanase in various disease states, including atherosclerosis formation and progression.Objective.The aim of the study was to investigate the effect of heparanase inhibition on blood pressure, blood glucose levels, and oxidative stress in apoE−/− mice.Methods.Male apoE−/− mice were divided into two groups: one treated by the heparanase inhibitor PG545, administered intraperitoneally weekly for seven weeks, and the other serving as control group (injected with saline). Blood pressure was measured a day before sacrificing the animals. Serum glucose levels and lipid profile were measured. Assessment of oxidative stress was performed as well.Results.PG545 significantly lowered blood pressure and serum glucose levels in treated mice. It also caused significant reduction of the serum oxidative stress. For safety concerns, liver enzymes were assessed, and PG545 caused significant elevation only of alanine aminotransferase, but not of the other hepatic enzymes.Conclusion.Heparanase inhibition by PG545 caused marked reduction of blood pressure, serum glucose levels, and oxidative stress in apolipoprotein E deficient mice, possibly via direct favorable metabolic and hemodynamic changes caused by the inhibitor. Possible hepatotoxic and weight wasting effects are subject for future investigation.

Enhanced Brain Delivery of Deferasirox–Lactoferrin Conjugates for Iron Chelation Therapy in Neurodegenerative Disorders: In Vitro and in Vivo Studies

2013 ◽  
Vol 10 (12) ◽  
pp. 4418-4431 ◽  
Author(s):  
Golnaz Kamalinia ◽  
Fariba Khodagholi ◽  
Fatemeh Atyabi ◽  
Mohsen Amini ◽  
Fatemeh Shaerzadeh ◽  
...  
Keyword(s):  
Neurodegenerative Disorders ◽  
Chelation Therapy ◽  
Iron Chelation ◽  
In Vivo Studies ◽  
Brain Delivery ◽  
Iron Chelation Therapy

scholarly journals Food-Derived Bioactive Peptides on Inflammation and Oxidative Stress

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Subhadeep Chakrabarti ◽  
Forough Jahandideh ◽  
Jianping Wu
Keyword(s):  
Oxidative Stress ◽  
Chronic Diseases ◽  
Bioactive Peptides ◽  
Antioxidant Properties ◽  
Food Proteins ◽  
Beneficial Effects ◽  
Pathological Conditions ◽  
Inflammatory Processes ◽  
Potential Benefits ◽  
And Oxidative Stress

Chronic diseases such as atherosclerosis and cancer are now the leading causes of morbidity and mortality worldwide. Inflammatory processes and oxidative stress underlie the pathogenesis of these pathological conditions. Bioactive peptides derived from food proteins have been evaluated for various beneficial effects, including anti-inflammatory and antioxidant properties. In this review, we summarize the roles of various food-derived bioactive peptides in inflammation and oxidative stress and discuss the potential benefits and limitations of using these compounds against the burden of chronic diseases.

scholarly journals Oxidative modification of glyceraldehyde-3-phosphate dehydrogenase influences its interaction with endogenous neuroprotector isatin

2016 ◽  
Vol 62 (2) ◽  
pp. 160-163 ◽  
Author(s):  
O.A. Buneeva ◽  
O.V. Gnedenko ◽  
M.V. Medvedeva ◽  
A.S. Ivanov ◽  
A.E. Medvedev
Keyword(s):  
Oxidative Stress ◽  
Surface Plasmon Resonance ◽  
Neurodegenerative Disorders ◽  
Redox State ◽  
Optical Biosensor ◽  
Oxidative Modification ◽  
Neuroprotective Agents ◽  
Putative Target ◽  
Parent Component ◽  
And Oxidative Stress

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a classical glycolytic redox sensitive enzyme, exhibits various non-glycolytic functions, which are considered to be especially important for progression of various neurodegenerative diseases. GAPDH binds isatin (indole-dione-2,3), an endogenous indole often used as a parent component in numerous derivatives demonstrating diverse pharmacological (including neuroprotector) activities. In this study we have investigated binding of intact and mildly oxidized GAPDH to immobilized isatin, using an optical biosensor technique, employing surface plasmon resonance (SPR), and the effect of isatin as a probe for this binding. Mild GAPDH oxidation by 70 mM H2O2 increased enzyme dissociation from immobilized isatin. Since GAPDH is considered as a putative target for various neuroprotector agents, this suggests that its redox state determines sensitivity to neuroprotective agents, and oxidative stress typical for various neurodegenerative disorders may significantly reduce pharmacological effectiveness of such compounds

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