Oxidative Stress: Neuropathy, Excitability, and ...repositorio.pucrs.br/.../13757/2/...Excitability_and_Neurodegeneration… · prevent neurodegeneration. The central nervous system

EditorialOxidative Stress: Neuropathy, Excitability,and Neurodegeneration

Alexandra Latini ,1 Paula Juliana Seadi Pereira,2 Réjean Couture,2Maria Martha Campos,3

and Sébastien Talbot 2

1LABOX, Departamento de Bioquímica, Universidade Federal de Santa Catarina, Florianópolis, SC 88040-900, Brazil2Département de Pharmacologie et Physiologie, Faculté de Médecine, Université de Montréal, Montréal, QC, Canada H3C 3J73School of Health Sciences, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS 90619-900, Brazil

Correspondence should be addressed to Sébastien Talbot; [email protected]

Received 2 December 2018; Accepted 11 December 2018; Published 6 January 2019

Copyright © 2019 Alexandra Latini et al. This is an open access article distributed under the Creative Commons AttributionLicense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work isproperly cited.

The energy produced from the aerobic cellular metabolismgenerates free radicals. The imbalance between the produc-tion of these radicals and their elimination via antioxidantdefenses leads tooxidative stress. The toxicity of these stressorscontributes to protein and DNA injury, inflammation, tissuedamage, and subsequent cellular apoptosis. Of note, neuronsare especially susceptible to reactive oxygen species- (ROS-)mediated damages. Thus, they have a very high demand inenergy, a large number of mitochondria, a limited capabilityto regulate glucose uptake, and weak antioxidant defenses.Alongside environmental and genetic factors, oxidativestress contributes to the onset of various pathologies suchas amyotrophic lateral sclerosis, Alzheimer’s disease, andParkinson’s disease, as well as diabetic-induced neuropathyand retinopathy. Thus, reduced antioxidant defenses, orthe overproduction or incorporation of free radicals fromthe environment, can lead to neurodegeneration. This spe-cial issue on “Oxidative Stress: Neuropathy, Excitability,and Neurodegeneration” aimed at addressing the physiol-ogy, the mechanisms, and the impact of oxidative stressin neuron excitability, neurodegeneration, retinopathy,and aging. Overall, this topic compiles seven quality scien-tific manuscripts including three research articles and fourcritical reviews, which provide comprehensive evidencedemonstrating the therapeutic significance of endogenous

and exogenous antioxidants in the control of neurodegen-erative pathologies.

Retinal detachment and blindness are increasingly morecommon and, while photocoagulation and anti-VEGFtherapy help control the onset of the disease, these patholo-gies remain largely intractable. To identify novel therapeutictargets for the treatment of retinopathy of prematurity,diabetic retinopathy, and age-related macular degeneration,Chemtob and colleagues provide a state-of-the-art reviewaddressing the role of oxidative stress and inflammatory pro-cesses in ischemic retinopathies. More specifically, theyassess how microvascular change-induced ischemia pro-motes abnormal neovascularization and how antioxidantsand anti-inflammatory agents emerged as novel therapeutictargets to reverse these ischemic retinopathies.

Kynurenic acid, one of the tryptophan metabolites, isincreased in the presence of free radicals and inflammatorycytokines and was shown to have neuroactive and redoxproperties. Through its action on NMDA and nicotinicreceptors, kynurenic acid is thought to modulate the releaseof neurotransmitters, and it was shown to regulate inflamma-tion in the context of aging, neurodegeneration, and psychiat-ric disorders. In this issue, Chavez and colleagues reviewedvarious alternative mechanisms through which kynurenicacid is produced, exploring the possible involvement of the

HindawiOxidative Medicine and Cellular LongevityVolume 2019, Article ID 2715326, 2 pageshttps://doi.org/10.1155/2019/2715326

http://orcid.org/0000-0003-4255-3589http://orcid.org/0000-0001-9932-7174https://creativecommons.org/licenses/by/4.0/https://creativecommons.org/licenses/by/4.0/https://doi.org/10.1155/2019/2715326

D-amino acid oxidase, indole-3-pyruvic acid, and myeloper-oxidase pathways, and how such paths may be exploited toprevent neurodegeneration.

The central nervous system possesses various pathwaysdesigned to control and protect the host from the exces-sive production of oxidative stress, one of which is thehydrogen sulfide pathway. Impairment in hydrogen sulfideproduction was posited to be an early trigger for Alzhei-mer’s, Parkinson’s, and Huntington’s diseases. The reviewarticle by Jung and colleagues discusses the antioxidantroles of hydrogen sulfide; how cystathionine β-synthase,cystathionine γ-lyase, cysteine aminotransferase, and3-mercaptopyruvate sulfurtransferase enzymatic activitiescontrol its production; and how neuroinflammation mightbe controlled through its antioxidant capability. Amongthe others, hydrogen sulfide helps maintain CNS homeostasisby shielding neurons against hypoxic injury, preventinghypochlorous acid-mediated oxidative damage, enhancingglutathione generation, and repressing mitochondrial oxida-tive stress.

The review of Kim and colleagues explores howglutathione S-transferase superfamily of enzymes mediatedcellular detoxification of oxidative damage. The omegasubfamily (GSTO) is the most recently identified memberof this class and appears to be expressed in a wide rangeof organisms including bacteria, insects, yeasts, mammals,and plants. GSTOs play an essential role in reducing theoxidative stress caused by stressors and cellular processes.Genetic polymorphisms in human GSTO1 and GSTO2genes have been implicated in neurodegenerative diseasessuch as Alzheimer’s and Parkinson’s, and the levels of GSTO2expression were described to be reduced in patients affectedby these pathologies. Altogether, by regulating theMAPK sig-naling pathway, GstO1 gene helps to prevent neurotoxicity.

The uncoupling proteins (UCPs) are anion-carrier pro-teins found in the inner membrane of the mitochondriaand are involved in the reduction of the transmembraneproton gradient. In this research paper, Antônio Silva Jrand colleagues explored whether UCP2 can protect neuronsfrom epilepsy-induced damage. The authors demonstratedthat the UCP2 mRNA expression was transiently increasedin the brain post status epilepticus. UCP2 antisense oligonu-cleotides significantly reduced the transcript expression ofUCP2 in SE-silent phase, preventing the expression ofp-AKT and antiapoptotic Bcl-2 mRNA. UCP2 silencing alsoincreases oxidative stress levels (reflected by augmented pro-tein carbonyl levels and the activity of the antioxidantenzymes superoxide dismutase, and catalase), the liberationof proinflammatory markers, and enhanced cell apoptosis.Overall, these data revealed that UPC2 might inhibit apopto-tic factors and oxidative stress in the pilocarpine model ofepilepsy, and, in doing so, reduced neurodegeneration.

Given that polyphenols help to prevent neurodegenera-tion, Eckert and colleagues assessed how highly purified olivesecoiridoids might abolish the cognitive decline typicallyobserved in aged mice. They found that a polyphenoltreatment prevented brain ATP reduction, as well as the tran-script expression of NADH reductase, cytochrome c oxidase,and citrate synthase. Overall, a diet rich in purified olive

polyphenols appears to protect from the decline in spatialworking memory and motor coordination observed in aging.Such protective phenomena appear to be mediated by theincrease in central ATP levels.

The colostrum is rich in nutrients crucial for newborndevelopment. The latter also contains bioactive peptides,which can help to control the oxidative damage observed inneurodegenerative diseases. In this research manuscript, thegroup of Prof. Zabłocka presents a novel method to isolateNP-POL nonapeptide from the milk colostrum. Next, byinhibiting ROS overproduction, they found that this peptideprotects PC12 cells from 6-hydroxydopamine-inducedneurotoxicity. Overall, these results suggest that theNP-POL nonapeptide may help prevent ROS-triggeredneurodegeneration.

Conflicts of Interest

The authors declare that there is no conflict of interestregarding the publication of this article.

Alexandra LatiniPaula Juliana Seadi Pereira

Réjean CoutureMaria Martha Campos

Sébastien Talbot

2 Oxidative Medicine and Cellular Longevity

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Oxidative Stress: Neuropathy, Excitability, and ...repositorio.pucrs.br/.../13757/2/...Excitability_and_Neurodegeneration… · prevent neurodegeneration. The central nervous system