Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5844019 | Pharmacology & Therapeutics | 2014 | 25 Pages |
Abstract
Oxidative stress is a common hallmark of neuronal cell death associated with neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, as well as brain stroke/ischemia and traumatic brain injury. Increased accumulation of reactive species of both oxygen (ROS) and nitrogen (RNS) has been implicated in mitochondrial dysfunction, energy impairment, alterations in metal homeostasis and accumulation of aggregated proteins observed in neurodegenerative disorders, which lead to the activation/modulation of cell death mechanisms that include apoptotic, necrotic and autophagic pathways. Thus, the design of novel antioxidant strategies to selectively target oxidative stress and redox imbalance might represent important therapeutic approaches against neurological disorders. This work reviews the evidence demonstrating the ability of genetically encoded antioxidant systems to selectively counteract neuronal cell loss in neurodegenerative diseases and ischemic brain damage. Because gene therapy approaches to treat inherited and acquired disorders offer many unique advantages over conventional therapeutic approaches, we discussed basic research/clinical evidence and the potential of virus-mediated gene delivery techniques for antioxidant gene therapy.
Keywords
6-OHDACOXIMSG6PDAADCbFGFNADPHGSHAβGPX6-HydroxydopamineCNTFGADGSSGNOSRNSCuZnSODAPPCBFIGF-1NGFLRRK2MPTPGCLGDNFΔΨmMnSODAAVAICDEAAT3-NPDMT1RAGETrxTrxRToMGCLCNTNVMAT2GCLMPRXGRxTBIGCH-1PSENMPOsMetSOONOOH1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine3-nitropropionic acidBDNFecSODEpREglutamic acid decarboxylaseNOxO2−ONOO−ROSSNpcTraumatic brain injurysuperoxide anionApoeapolipoprotein ENeurodegenerative disordersamyotrophic lateral sclerosisPeroxynitrous acidtranslocase of the outer membraneNADPH oxidaseOxygenBrain ischemiaAlzheimer's diseaseALSHuntington's diseaseParkinson's diseasethioredoxin reductaseOxidative stresssubstantia nigra pars compactathioredoxintyrosine hydroxylasecerebral blood flowVesicular monoamine transporterexcitatory amino acid transporterAmyloid precursor protein intracellular domainHydroxyl radicalelectron transport chainBBBextracellular superoxide dismutaseCopper-zinc superoxide dismutasemanganese superoxide dismutasesuperoxide dismutasesMethionine sulfoxideCyclooxygenasesInsulin growth factor 1antioxidant response elementGranulocyte-colony stimulating factorVascular endothelial growth factorVascular Endothelial Growth Factor (VEGF)nerve growth factorbasic fibroblast growth factorG-CSFGlial-cell-line-derived neurotrophic factorciliary neurotrophic factorBlood-brain barrierCerebrospinal fluidCSFDivalent metal transporter 1neurturinnitric oxide synthasenicotinamide adenine dinucleotide phosphatemutant HuntingtinAREHeme-oxygenaseETcAdeno-associated virusLentivirusSODsMitochondrial membrane potentialPresenilinamyloid precursor proteinPeroxiredoxinPeroxynitriteamyloid-β peptideglutamate-cysteine ligase modifier subunitglutamate-cysteine ligase catalytic subunitleucine rich repeat kinase 2Glutathioneglutathione disulfideglutathione reductaseGlutathione peroxidasesGlutaredoxinglucose-6-phosphate dehydrogenasereactive nitrogen speciesReactive oxygen speciesReceptor for advanced glycation end products
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Authors
Juliana Navarro-Yepes, Laura Zavala-Flores, Annadurai Anandhan, Fang Wang, Maciej Skotak, Namas Chandra, Ming Li, Aglaia Pappa, Daniel Martinez-Fong, Luz Maria Del Razo, Betzabet Quintanilla-Vega, Rodrigo Franco,