)| PMID |
10525172 ( ) |
|---|---|
| Title | Neurodegenerative disorders: the role of peroxynitrite. |
| Abstract | Inflammatory reaction is thought to be an important contributor to neuronal damage in neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS) and the parkinsonism dementia complex of Guam. Among the toxic agents released in brain tissues by activated cells, we focus attention in this review on peroxynitrite, the product of the reaction between nitric oxide (NO) and superoxide. Peroxynitrite is a strong oxidizing and nitrating agent which can react with all classes of biomolecules. In the CNS it can be generated by microglial cells activated by pro-inflammatory cytokines or beta-amyloid peptide (beta-A) and by neurons in three different situations: hyperactivity of glutamate neurotransmission, mitochondrial dysfunction and depletion of L-arginine or tetrahydrobiopterin. The first two situations correspond to cellular responses to an initial neuronal injury and the peroxynitrite formed only exacerbates the inflammatory process, whereas in the third situation the peroxynitrite generated directly contributes to the initiation of the neurodegenerative process. France. |
NOTE: Color highlight is limited to the abstract and SciMiner text-mining mode. If you see much more identified targets below from "Targets by SciMiner Summary" and "Targets by SciMiner Full list", they may have been identified from the full text.
Targets by SciMiner Summary
| HUGO ID | Symbol | Target Name | #Occur | ActualStr |
|---|---|---|---|---|
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | 37 | NOS | NOSs | NOS-catalyzed | NOS-transfected | |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | 13 | SOD | superoxide dismutase | |
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | 7 | APP | amyloid | |
| 7739 | NEFL | neurofilament, light polypeptide 68kDa | 4 | nf l | NF-L | |
| 6018 | IL6 | interleukin 6 (interferon, beta 2) | 2 | IL-6 | il 6 | |
| 5992 | IL1B | interleukin 1, beta | 2 | IL-1 | il 1 | |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | 2 | nadph oxidase | |
| 1033 | BDNF | brain-derived neurotrophic factor | 2 | brain derived neurotrophic factor | BDNF | |
| 727 | ARTN | artemin | 1 | neurotrophic factor | |
| 758 | ASS1 | argininosuccinate synthetase 1 | 1 | argininosuccinate synthetase | |
| 746 | ASL | argininosuccinate lyase | 1 | argininosuccinate lyase | |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | 1 | nitric oxide synthase | |
| 11782 | TH | tyrosine hydroxylase | 1 | tyrosine hydroxylase | |
| 3768 | FMN1 | formin 1 | 1 | FMN | |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | 1 | TNF | |
| 31395 | COX8B | cytochrome c oxidase, subunit 8B pseudogene | 1 | cytochrome c oxidase | |
| 4623 | GSR | glutathione reductase | 1 | glutathione reductase | |
Targets by SciMiner Full list
| HUGO ID | Symbol | Name | ActualStr | Score | FlankingText |
|---|---|---|---|---|---|
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | amyloid | 1.0 | generated by microglial cells activated by pro-inflammatory cytokines or _amp_#x3b2 -amyloid peptide (_amp_#x3b2;-A) _amp_#x3b2 -A and by neurons in three different |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 1.4 | with O 2 _amp_#x2212 three-fold faster than superoxide dismutase (SOD) SOD ( k =2.3_amp_#xd7 10 9 M _amp_#x2212 1 s _amp_#x2212 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 1.4 | NO is the only known biomolecule capable of out competing SOD for available O 2 _amp_#x2212 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 1.4 | Because the concentrations of SOD and O 2 _amp_#x2212 in a given tissue are relatively |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS | 3.0 | In the CNS three NO-synthase isoforms neuronal Type-I NOS inducible Type-II NOS and endothelial Type-III NOS can generate NO |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS | 3.0 | the CNS three NO-synthase isoforms neuronal Type-I NOS inducible Type-II NOS and endothelial Type-III NOS can generate NO |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS | 3.0 | isoforms neuronal Type-I NOS inducible Type-II NOS and endothelial Type-III NOS can generate NO |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOSs | 1.2 | great deal of detail about the biochemistry and pharmacology of NOSs as there are many excellent review articles 53 78 80 |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS | 3.0 | Type-I NOS has been detected in the cerebellum the hypothalamus the striatum |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS | 3.0 | Type-II NOS is located predominantly in microglia and astrocytes 43 |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS | 3.0 | Type-III NOS has been detected in microvessels and motor neurons from rodents |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS | 3.0 | By reaction of NO from Type-I NOS with O 2 _amp_#x2212 from the mitochondrial respiratory chain |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 1.4 | be unlikely since Okabe et al 65 recently shown that SOD the enzyme which scavengers O 2 _amp_#x2212 colocalizes with NOS |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS | 3.0 | SOD the enzyme which scavengers O 2 _amp_#x2212 colocalizes with NOS in the hippocampus and the cerebellum where NO plays an |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS | 3.0 | abnormal activation of Ca 2 -dependent enzymes including the Type-I NOS |
| 5992 | IL1B | interleukin 1, beta | IL-1 | 1.0 | Microglial cells can be activated by pro-inflammatory cytokines IL-1 IL-6 and TNF_amp_#x3b1 as well as by _amp_#x3b2 -amyloid peptide |
| 6018 | IL6 | interleukin 6 (interferon, beta 2) | IL-6 | 1.0 | Microglial cells can be activated by pro-inflammatory cytokines IL-1 IL-6 and TNF_amp_#x3b1 as well as by _amp_#x3b2 -amyloid peptide (_amp_#x3b2;-A) |
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | amyloid | 1.0 | cytokines IL-1 IL-6 and TNF_amp_#x3b1 as well as by _amp_#x3b2 -amyloid peptide (_amp_#x3b2;-A) _amp_#x3b2 -A 82 90 the first 42 amino |
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | amyloid | 1.0 | _amp_#x3b2 -A 82 90 the first 42 amino acids of amyloid precursor protein (APP) APP ( Fig 6 |
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | APP | 0.3 | the first 42 amino acids of amyloid precursor protein (APP) APP ( Fig 6 |
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | amyloid | 1.0 | and thus peroxynitrite the soluble _amp_#x3b2 -A monomer a diffuse amyloid deposit and mature filamentous amyloid plaques |
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | amyloid | 1.0 | _amp_#x3b2 -A monomer a diffuse amyloid deposit and mature filamentous amyloid plaques |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS | 3.0 | on microglia cultures Walker et al 89 by measuring Type-I NOS gene expression on human microglia cultures and Vodovotz et al |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS | 3.0 | the blood_amp_#x2013 brain barrier associated with enhanced expression of Type-III NOS in microvessels and the presence of numerous inducible Type-II NOS |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS | 3.0 | NOS in microvessels and the presence of numerous inducible Type-II NOS immunoreactive microglia |
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | amyloid | 1.0 | a pathway for peroxynitrite formation may be postulated in cerebral amyloid angiopathy which is frequently associated with AD 84 93 |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS | 3.0 | By Type-I NOS activity in arginine- or tetrahydrobiopterin-depleted conditions |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS | 3.0 | Type-I NOS and Type-II NOS catalyze electron transfer from NADPH to O |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS | 3.0 | Type-I NOS and Type-II NOS catalyze electron transfer from NADPH to O 2 in the |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS | 3.0 | At low arginine concentrations 62 67 however Type-II NOS strongly reduces the NADPH oxidation rate while Type-I NOS still |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS | 3.0 | Type-II NOS strongly reduces the NADPH oxidation rate while Type-I NOS still oxidizes NADPH with an unmodified rate and then reduces |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS-transfected | 1.2 | a 20-fold increase of O 2 _amp_#x2212 formation in Type-I NOS-transfected human kidney 293 cells as the cytosolic -arginine levels decreased |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS | 3.0 | The NOS inhibitor N -nitro--arginine methyl ester virtually abolished the O 2 |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS | 3.0 | Therefore at low arginine concentrations Type-I NOS produces simultaneously O 2 _amp_#x2212 and NO at the same |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS | 3.0 | by Gorren and Mayer 32 in a study of Type-I NOS activity as a function of tetrahydrobiopterin (BH BH 4 concentration |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS | 3.0 | Type-I NOS is a dimeric enzyme which exhibits strong anti-cooperative binding of |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS | 3.0 | 10 _amp_#x2212 9 M no BH 4 molecule binds Type-I NOS and O 2 _amp_#x2212 is produced whereas at high BH |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 1.4 | 1993 Beckman et al 8 pointed out that mutations in SOD associated with the autosomal dominant inheritance of familial ALS could |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 1.4 | the steady state concentration of O 2 _amp_#x2212 by decreasing SOD activity by 50% and increase nitration of critical cellular targets |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 1.4 | peroxynitrite to copper a strong tyrosyl nitration catalysis in the SOD active site |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 1.4 | by the demonstration that the zinc affinity of four ALS-associated SOD mutants was decreased up to 30-fold compared with wild-type SOD |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 1.4 | SOD mutants was decreased up to 30-fold compared with wild-type SOD |
| 7739 | NEFL | neurofilament, light polypeptide 68kDa | NF-L | 1.3 | These investigators also showed that the motor neuron protein neurofilament- NF-L could bind zinc atoms with sufficient affinity to potentially remove |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 1.4 | zinc atoms with sufficient affinity to potentially remove zinc from SOD and that the loss of zinc from wild-type SOD almost |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 1.4 | from SOD and that the loss of zinc from wild-type SOD almost doubled the efficiency of this enzyme for catalyzing for |
| 7739 | NEFL | neurofilament, light polypeptide 68kDa | NF-L | 1.3 | no significant qualitative or quantitative modifications in the nitrotyrosine-immunoreactivity of NF-L isolated from sporadic ALS cervical spinal cord tissue as compared |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS | 3.0 | of mice with EAE by Lin et al 51 Type-II NOS mRNA has been detected in EAE models by Cross et |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF | 0.3 | an overexpression of the proinflammatory cytokines IL1-_amp_#x3b2 IL2 IFN_amp_#x3b3 and TNF and a defective production of the anti-inflammatory cytokine TGF-_amp_#x3b2 associated |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS | 3.0 | the anti-inflammatory cytokine TGF-_amp_#x3b2 associated with an increase in Type-II NOS mRNA expression and nitrite production in peripheral blood mononuclear cells |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS | 3.0 | Beal 7 reported the protective effect of Type-I NOS inhibitors on the neurotoxicity of MPTP in both mice and |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS | 3.0 | Under normal conditions neurons produce NO via Type-I NOS as an intracellular messenger which has an important role in |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS | 3.0 | contrary under either -arginine- or BH 4 -depleted conditions Type-I NOS monomers can function independently of each other |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS | 3.0 | second step of the neurodegenerative process by induction of Type-II NOS which produces large amounts of NO and stimulation of NADPH-oxidase |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS | 3.0 | Type-III NOS expressed in microvessels and motor neurons can also generate NO |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS | 3.0 | These authors observed an expression of Type-III NOS but not of Type-I NOS by motor neurons cultured with |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS | 3.0 | observed an expression of Type-III NOS but not of Type-I NOS by motor neurons cultured with brain-derived neurotrophic factor (BDNF) BDNF |
| 1033 | BDNF | brain-derived neurotrophic factor | BDNF | 1.9 | NOS by motor neurons cultured with brain-derived neurotrophic factor (BDNF) BDNF |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS | 3.0 | On the contrary trophic factor deprivation promoted Type-I NOS expression and cell death by apoptosis |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS | 3.0 | motor neuron degeneration was promoted by NO produced by Type-I NOS and reversed by SOD suggesting that formation of peroxynitrite initiates |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 1.4 | promoted by NO produced by Type-I NOS and reversed by SOD suggesting that formation of peroxynitrite initiates apoptosis |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS | 3.0 | mechanism we described previously for generation of peroxynitrite by Type-I NOS under -arginine- or BH 4 -depleted conditions |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS-catalyzed | 1.2 | Schematic representation of NOS-catalyzed reactions |
| 3768 | FMN1 | formin 1 | FMN | 0.2 | -arginine NADPH and O 2 and require five cofactors FAD FMN calmodulin (CaM), CaM tetrahydrobiopterin (BH BH 4 and heme |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | superoxide dismutase | 1.0 | because nitric oxide reacts with o 2 _amp_#x2212; three fold faster than superoxide dismutase sod k =2.3_amp_#xd7;10 9 m _amp_#x2212;1 s _amp_#x2212;1 no is the only known biomolecule capable of out competing sod for available o 2 _amp_#x2212; . |
| 746 | ASL | argininosuccinate lyase | argininosuccinate lyase | 1.0 | the citrulline formed can leave the cell or be converted back to arginine via the enzymes argininosuccinate lyase located in bergmann glia and argininosuccinate synthetase located in basket cells stellate cells golgi cells and mossy fibers. |
| 758 | ASS1 | argininosuccinate synthetase 1 | argininosuccinate synthetase | 1.0 | the citrulline formed can leave the cell or be converted back to arginine via the enzymes argininosuccinate lyase located in bergmann glia and argininosuccinate synthetase located in basket cells stellate cells golgi cells and mossy fibers. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | be formed as a by product of the mitochondrial respiratory chain generated primarily by autoxidation of flavoproteins [ 78 ] fig 4 or during the respiratory burst of phagocytes via the activation of nadph oxidase [ 48 ]. |
| 31395 | COX8B | cytochrome c oxidase, subunit 8B pseudogene | cytochrome c oxidase | 1.0 | moreover excess no may also promote an increase of o 2 _amp_#x2212; production by binding to the heme moiety of the cytochrome c oxidase the complex iv of the electron transport chain in the mitochondrial membrane. |
| 5992 | IL1B | interleukin 1, beta | il 1 | 1.0 | microglial cells can be activated by pro inflammatory cytokines il 1 il 6 and tnf_amp_#x3b1; as well as by _amp_#x3b2; amyloid peptide _amp_#x3b2; a [ 82 90 ] the first 42 amino acids of amyloid precursor protein app fig 6 . |
| 6018 | IL6 | interleukin 6 (interferon, beta 2) | il 6 | 1.0 | microglial cells can be activated by pro inflammatory cytokines il 1 il 6 and tnf_amp_#x3b1; as well as by _amp_#x3b2; amyloid peptide _amp_#x3b2; a [ 82 90 ] the first 42 amino acids of amyloid precursor protein app fig 6 . |
| 7739 | NEFL | neurofilament, light polypeptide 68kDa | nf l | 1.0 | these investigators also showed that the motor neuron protein neurofilament nf l could bind zinc atoms with sufficient affinity to potentially remove zinc from sod and that the loss of zinc from wild type sod almost doubled the efficiency of this enzyme for catalyzing for peroxyn |
| 7739 | NEFL | neurofilament, light polypeptide 68kDa | nf l | 1.0 | however strong et al. [ 81 ] recently reported that there were no significant qualitative or quantitative modifications in the nitrotyrosine immunoreactivity of nf l isolated from sporadic als cervical spinal cord tissue as compared with age matched non als controls. |
| 11782 | TH | tyrosine hydroxylase | tyrosine hydroxylase | 1.0 | ara et al. [ 3 ] observed the inactivation of tyrosine hydroxylase by nitration following exposure of pc 12 cells to either peroxynitrite or mptp. |
| 4623 | GSR | glutathione reductase | glutathione reductase | 1.0 | barker et al. [ 5 ] demonstrated the susceptibility of glutathione reductase the enzyme which regenerates glutathione from its oxidized form to peroxynitrite. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | s primary neuronal insult can activate microglial cells and initiate the second step of the neurodegenerative process by induction of type ii nos which produces large amounts of no and stimulation of nadph oxidase which produces o 2 _amp_#x2212; . |
| 727 | ARTN | artemin | neurotrophic factor | 1.0 | these authors observed an expression of type iii nos but not of type i nos by motor neurons cultured with brain derived neurotrophic factor bdnf . |
| 1033 | BDNF | brain-derived neurotrophic factor | brain derived neurotrophic factor | 1.0 | these authors observed an expression of type iii nos but not of type i nos by motor neurons cultured with brain derived neurotrophic factor bdnf . |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | nitric oxide synthase | 1.0 | schematic representation of the nitric oxide synthase monomer. |