Mitochondria-targeted antioxidants for treatment of Parkinson’s disease: Preclinical and clinical outcomes.
Misfolded Proteins, Mitochondrial Dysfunction, and Neurodegenerative Diseases
Jin H1, Kanthasamy A, Ghosh A, Anantharam V, Kalyanaraman B, Kanthasamy AG
1 Parkinson’s Disorder Research Laboratory, Iowa Center for Advanced Neurotoxicology, Department of Biomedical Sciences, Iowa State University, Ames, IA 50011, USA.
Abstract
Parkinson’s disease is a progressive neurodegenerative disease in the elderly, and no cure or disease-modifying therapies exist. Several lines of evidence suggest that mitochondrial dysfunction and oxidative stress have a central role in the dopaminergic neurodegeneration of Parkinson’s disease. In this context, mitochondria-targeted therapies that improve mitochondrial function may have great promise in the prevention and treatment of Parkinson’s disease. In this review, we discuss the recent developments in mitochondria-targeted antioxidants and their potential beneficial effects as a therapy for ameliorating mitochondrial dysfunction in Parkinson’s disease. This article is part of a Special Issue entitled: Misfolded Proteins, Mitochondrial Dysfunction and Neurodegenerative Diseases.
Fig. 1. Schematic presentation of the generation of ROS in mitochondria. ROS are generated from the transfer of electrons (e−) to molecular oxygen to form superoxide (O2•−) at the mitochondrial electron transport chain complexes I and III. Once generated, superoxide is decomposed enzymatically by superoxide dismutase 1 (SOD1) in the intermembrane space and by SOD2 (MnSOD) in the matrix to form hydrogen peroxide, which is further catabolized to water by the action of enzymes such as catalase (CAT), glutathione peroxidases (GPx), and thioredoxin reductase (TPx) to avoid possible buildup of oxidative stress. However, under mitochondrial stress, superoxide may react with nitric oxide to form the potent oxidant and nitrating agent peroxynitrite (ONOO−). Hydrogen peroxide can also form the highly reactive hydroxyl radical (OH•) in the presence of Fe2+ cations. These highly reactive radicals may cause damage to proteins, lipids, and nucleic acids. CoQ, coenzyme Q; Cyt C, cytochrome C.
