Oxidative Stress in Neurodegenerative Diseases

Abstract

The pathophysiologies of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), and Alzheimer's disease (AD), are far from being fully explained. Oxidative stress (OS) has been proposed as one factor that plays a potential role in the pathogenesis of neurodegenerative disorders. Clinical and preclinical studies indicate that neurodegenerative diseases are characterized by higher levels of OS biomarkers and by lower levels of antioxidant defense biomarkers in the brain and peripheral tissues. In this article, we review the current knowledge regarding the involvement of OS in neurodegenerative diseases, based on clinical trials and animal studies. In addition, we analyze the effects of the drug-induced modulation of oxidative balance, and we explore pharmacotherapeutic strategies for OS reduction.

Keywords: Alzheimer’s disease; Amyotrophic lateral sclerosis; Antioxidant defense molecule; ESR—electron spin resonance; IST—immuno-spin trapping technique; Non-enzymatic and enzymatic antioxidant; Oxidative stress biomarker; Parkinson’s disease.

Fig. 1

Generation of reactive species (based on [–283])

Fig. 2

Source of radical and OS biomarkers. 8-OHA 2,8-hydroxyadenine, HNE 4-hydroxynonenal, 5-OHC 5-hydroxycytosine, 5-OHU 5-hydroxyuracil, 8-OHdG 8-hydroxy-2′-deoxyguanosine, 8-OH-Gua 8-hydroxyguanine, AGEs advanced glycation end products, ALES advanced lipid peroxidation end products, AOPP advanced oxidation products, CTL creatol, COX cyclooxygenases, CYP cytochrome P450, ETC electron transport chain, F2-isoPs F2-isoprostanes, F4-NPs F 4-neuroprostanes, HETE hydroxyeicosatetraenoic acids, HODE hydroxyoctadecadienoic acid, HIF-1a hypoxia-inducible factor-1a, IsoF isofuran, LF lipofuscin, LOX lipoxygenases, Lyso PC lysophosphatidylcholines, MPO myeloperoxidase, NOX NADPH oxidases, NFS neurofuran, Opht A ophthalmic acid, GSSG oxidized glutathione, ox-LDL oxidized LDL, GSSG/GSH oxidized/reduced glutathione, Prxs peroxiredoxins, PC protein carbonyl, TBARS thiobarbituric acid reactive substances, TQ/TQH2 tocopherylquinone/tocopheryl hydroquinone, TAC total antioxidant capacity, Tyr tyrosines, UQ/UQH2 ubiquinone/ubiquinol, XO xanthine oxidase