Abstract
Parkinson’s disease (PD) is related to excess production of reactive oxygen species (ROS) or inadequate and impaired detoxification by endogenous antioxidants, alterations in catecholamine metabolism, alterations in mitochondrial electron transfer function, and enhanced iron deposition in the substantia nigra. The concept that oxidative stress is an important mechanism underlying the degeneration of dopaminergic (DAergic) neurons is reinforced by data documenting that high levels of lipid peroxidation, increased oxidation of proteins and DNA and depletion of glutathione are observed in postmortem studies of brain tissues of PD patients. Tyrosine hydroxylase (TH) is an important neuronal enzyme that, in the presence of tetrahydrobiopterin, catalyzes the initial and rate-limiting step in the biosynthesis of the catecholamine neurotransmitters dopamine (DA) and norepinephrine, and is frequently used as a marker of DAergic neuronal loss in animal models of PD. The role for TH as generators of ROS are highly relevant to PD because ROS have been proposed to contribute to the neurodegeneration of DA neurons. Oxidants and superoxide radicals are produced as byproducts of oxidative phosphorylation, making mitochondria the main site of ROS generation within the cell and the site of the first line of defence against oxidative stress. ROS can affect mitochondrial DNA (mtDNA) causing modulation in synthesis of electron transport chain (ETC) components, decreased ATP production, and increased leakage of ROS.
Keywords: Parkinson's disease, oxidative stress, mitochondria, tyrosine hydroxylase.
CNS & Neurological Disorders - Drug Targets
Title:Mitochondria as an Easy Target to Oxidative Stress Events in Parkinson's Disease
Volume: 11 Issue: 4
Author(s): Marcella Reale, Mirko Pesce, Medha Priyadarshini, Mohammad A Kamal and Antonia Patruno
Affiliation:
Keywords: Parkinson's disease, oxidative stress, mitochondria, tyrosine hydroxylase.
Abstract: Parkinson’s disease (PD) is related to excess production of reactive oxygen species (ROS) or inadequate and impaired detoxification by endogenous antioxidants, alterations in catecholamine metabolism, alterations in mitochondrial electron transfer function, and enhanced iron deposition in the substantia nigra. The concept that oxidative stress is an important mechanism underlying the degeneration of dopaminergic (DAergic) neurons is reinforced by data documenting that high levels of lipid peroxidation, increased oxidation of proteins and DNA and depletion of glutathione are observed in postmortem studies of brain tissues of PD patients. Tyrosine hydroxylase (TH) is an important neuronal enzyme that, in the presence of tetrahydrobiopterin, catalyzes the initial and rate-limiting step in the biosynthesis of the catecholamine neurotransmitters dopamine (DA) and norepinephrine, and is frequently used as a marker of DAergic neuronal loss in animal models of PD. The role for TH as generators of ROS are highly relevant to PD because ROS have been proposed to contribute to the neurodegeneration of DA neurons. Oxidants and superoxide radicals are produced as byproducts of oxidative phosphorylation, making mitochondria the main site of ROS generation within the cell and the site of the first line of defence against oxidative stress. ROS can affect mitochondrial DNA (mtDNA) causing modulation in synthesis of electron transport chain (ETC) components, decreased ATP production, and increased leakage of ROS.
Export Options
About this article
Cite this article as:
Reale Marcella, Pesce Mirko, Priyadarshini Medha, A Kamal Mohammad and Patruno Antonia, Mitochondria as an Easy Target to Oxidative Stress Events in Parkinson's Disease, CNS & Neurological Disorders - Drug Targets 2012; 11 (4) . https://dx.doi.org/10.2174/187152712800792875
DOI https://dx.doi.org/10.2174/187152712800792875 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
Call for Papers in Thematic Issues
Diagnosis and treatment of central nervous system infectious diseases
Infectious diseases of the central nervous system (CNS) can be divided into bacterial, tuberculous, viral, fungal, parasitic infections, etc. Early etiological treatment is often the most crucial means to reduce the mortality rate of patients with central nervous system infections, reduce complications and sequelae, and improve prognosis. The initial clinical ...read more
Techniques of Drug Repurposing: Delivering a new life to Herbs & Drugs
Of late, with the adaptation of innovative approaches and integration of advancements made towards medical sciences as well as the availability of a wide range of tools; several therapeutic challenges are being translated into viable clinical solutions, with a high degree of efficacy, safety, and selectivity. With a better understanding ...read more
Trends and perspectives in the rational management of CNS disorders
Central nervous system (CNS) diseases enforce a significant global health burden, driving ongoing efforts to improve our understanding and effectiveness of therapy. This issue investigates current advances in the discipline, focusing on the understanding as well as therapeutic handling of various CNS diseases. The issue covers a variety of diseases, ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Isosteviol as a Starting Material in Organic Synthesis
Current Organic Chemistry The Role of 18 kDa Mitochondrial Translocator Protein (TSPO) in Programmed Cell Death, and Effects of Steroids on TSPO Expression
Current Molecular Medicine Activated Protein C: A Promising Drug with Multiple Effects?
Mini-Reviews in Medicinal Chemistry 5-Aminoisoquinolin-1-one (5-AIQ), a Water-Soluble Inhibitor of the Poly(ADP-Ribose)Polymerases (PARPs)
Current Medicinal Chemistry Disruption of Circadian Rhythms and Sleep in Critical Illness and its Impact on Innate Immunity
Current Pharmaceutical Design Cannabinoid System in Neurodegeneration: New Perspectives in Alzheimers Disease
Mini-Reviews in Medicinal Chemistry Pharmacologic Modulators of Soluble Guanylate Cyclase/Cyclic Guanosine Monophosphate in the Vascular System - From Bench Top to Bedside
Current Vascular Pharmacology Phospholipase A2 Isoforms as Novel Targets for Prevention and Treatment of Inflammatory and Oncologic Diseases
Current Drug Targets Gene-based Therapeutic Tools in the Treatment of Cornea Disease
Current Gene Therapy Effect of Edaravone on MicroRNA Expression in Exosomes after Hepatic Ischemia-reperfusion Injury
Current Molecular Pharmacology Contribution of Canalicular Glutathione Efflux to Bile Formation. From Cholestasis Associated Alterations to Pharmacological Intervention to Modify Bile Flow
Current Drug Targets - Immune, Endocrine & Metabolic Disorders Molecular and Cellular Pathways as a Target of Therapeutic Hypothermia: Pharmacological Aspect
Current Neuropharmacology Mechanisms of Platelet Activation in Acute Coronary Syndromes
Current Vascular Pharmacology Pharmacological Potential of Tetrahydrofurano/Pyrano Quinoline and Benzo[b]furoindolyl Derivatives in Acute Inflammation, Pain and Oxidative Stress
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry The Role of Matrix Metalloproteinases in Diabetes Mellitus
Current Topics in Medicinal Chemistry New Generation Calcium Channel Blockers in Hypertensive Treatment
Current Hypertension Reviews Beta Blocker Use After Acute Myocardial Infarction in the Patient with Normal Systolic Function: When is it “Ok” to Discontinue?
Current Cardiology Reviews Oxyprenylated Secondary Metabolites as Modulators of Lipid and Sugar Metabolism
Current Topics in Medicinal Chemistry An Integrated In Silico Method to Discover Novel Rock1 Inhibitors: Multi- Complex-Based Pharmacophore, Molecular Dynamics Simulation and Hybrid Protocol Virtual Screening
Combinatorial Chemistry & High Throughput Screening Pharmacology and Therapeutic Applications of A1 Adenosine Receptor Ligands
Current Topics in Medicinal Chemistry