Dataset Information

Oxidative Stress: Mechanistic Insights into Inherited Mitochondrial Disorders and Parkinson's Disease.

ABSTRACT: Oxidative stress arises when cellular antioxidant defences become overwhelmed by a surplus generation of reactive oxygen species (ROS). Once this occurs, many cellular biomolecules such as DNA, lipids, and proteins become susceptible to free radical-induced oxidative damage, and this may consequently lead to cellular and ultimately tissue and organ dysfunction. Mitochondria, as well as being a source of ROS, are vulnerable to oxidative stress-induced damage with a number of key biomolecules being the target of oxidative damage by free radicals, including membrane phospholipids, respiratory chain complexes, proteins, and mitochondrial DNA (mt DNA). As a result, a deficit in cellular energy status may occur along with increased electron leakage and partial reduction of oxygen. This in turn may lead to a further increase in ROS production. Oxidative damage to certain mitochondrial biomolecules has been associated with, and implicated in the pathophysiology of a number of diseases. It is the purpose of this review to discuss the impact of such oxidative stress and subsequent damage by reviewing our current knowledge of the pathophysiology of several inherited mitochondrial disorders together with our understanding of perturbations observed in the more commonly acquired neurodegenerative disorders such as Parkinson's disease (PD). Furthermore, the potential use and feasibility of antioxidant therapies as an adjunct to lower the accumulation of damaging oxidative species and hence slow disease progression will also be discussed.

SUBMITTER: Al Shahrani M

PROVIDER: S-EPMC5704117 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Oxidative Stress: Mechanistic Insights into Inherited Mitochondrial Disorders and Parkinson's Disease.

Al Shahrani Mesfer M Heales Simon S Hargreaves Iain I Orford Michael M

Journal of clinical medicine 20171027 11

Oxidative stress arises when cellular antioxidant defences become overwhelmed by a surplus generation of reactive oxygen species (ROS). Once this occurs, many cellular biomolecules such as DNA, lipids, and proteins become susceptible to free radical-induced oxidative damage, and this may consequently lead to cellular and ultimately tissue and organ dysfunction. Mitochondria, as well as being a source of ROS, are vulnerable to oxidative stress-induced damage with a number of key biomolecules bein ...[more]

PMID: 29077060

Similar Datasets

Project description:The mucolytic agent S-carboxymethylcysteine is widely used as an expectorant for the treatment of numerous respiratory disorders. The metabolic fate of S-carboxymethyl-L-cysteine is complex. Several clinical studies have demonstrated that the metabolism of this agent differs within the same individual, with sulfur oxygenated metabolites generated upon night-time administration. It has been indicated that this drug behaves like a free radical scavenger and that, in this regard, the sulfide is the active species with sulphoxide metabolites (already oxidized) being inactive. Consequently, a night-time consumption of the drug should be more effective upon daytime administration. Still, this diurnal variation in biotransformation (deactivation) is dependent on the genetic polymorphism on which relies the patient population capacities of S-carboxymethyl-L-cysteine sulphoxidation. It has been reported that those cohorts who are efficient sulfur oxidizers will generate inactive oxygenated metabolites. In contrast, those who have a relative deficiency in this mechanism will be subjected to the active sulfide for a more extended period. In this regard, it is noteworthy that 38-39% of Parkinson's disease patients belong to the poor sulphoxide cohort, being exposed to higher levels of active sulfide, the active antioxidant metabolite of S-carboxymethyl-L-cysteine. Parkinson's disease is a neurodegenerative disorder that affects predominately dopaminergic neurons. It has been demonstrated that oxidative stress and mitochondrial dysfunction play a crucial role in the degeneration of dopaminergic neurons. Based on this evidence, in this study, we evaluated the effects of S-carboxymethyl cysteine in an in vitro model of Parkinson's disease in protecting against oxidative stress injury. The data obtained suggested that an S-carboxymethylcysteine-enriched diet could be beneficial during aging to protect neurons from oxidative imbalance and mitochondrial dysfunction, thus preventing the progression of neurodegenerative processes.

Dataset Information

Oxidative Stress: Mechanistic Insights into Inherited Mitochondrial Disorders and Parkinson's Disease.

Publications

Oxidative Stress: Mechanistic Insights into Inherited Mitochondrial Disorders and Parkinson's Disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets