)| PMID |
12893007 ( ) |
|---|---|
| Title | 4-hydroxynonenal and neurodegenerative diseases. |
| Abstract | The development of oxidative stress, in which production of highly reactive oxygen species (ROS) overwhelms antioxidant defenses, is a feature of many neurological diseases: ischemic, inflammatory, metabolic and degenerative. Oxidative stress is increasingly implicated in a number of neurodegenerative disorders characterized by abnormal filament accumulation or deposition of abnormal forms of specific proteins in affected neurons, like Alzheimer's disease (AD), Pick's disease, Lewy bodies related diseases, amyotrophic lateral sclerosis (ALS), and Huntington disease. Causes of neuronal death in neurodegenerative diseases are multifactorial. In some familiar cases of ALS mutation in the gene for Cu/Zn superoxide dismutase (SOD1) can be identified. In other neurodegenerative diseases ROS have some, usually not clear, role in early pathogenesis or implications on neuronal death in advanced stages of illness. The effects of oxidative stress on "post-mitotic cells", such as neurons may be cumulative, hence, it is often unclear whether oxidative damage is a cause or consequence of neurodegeneration. Peroxidation of cellular membrane lipids, or circulating lipoprotein molecules generates highly reactive aldehydes among which one of most important is 4-hydroxynonenal (HNE). The presence of HNE is increased in brain tissue and cerebrospinal fluid of AD patients, and in spinal cord of ALS patients. Immunohistochemical studies show presence of HNE in neurofibrilary tangles and in senile plaques in AD, in the cytoplasm of the residual motor neurons in sporadic ALS, in Lewy bodies in neocortical and brain stem neurons in Parkinson's disease (PD) and in diffuse Lewy bodies disease (DLBD). Thus, increased levels of HNE in neurodegenerative disorders and immunohistochemical distribution of HNE in brain tissue indicate pathophysiological role of oxidative stress in these diseases, and especially HNE in formation of abnormal filament deposites. Clinical Medical, Center Zagreb, Kispaticeva 12, 10000 Zagreb, Croatia. kamelijazarkovic@yahoo.com |
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 |
|---|---|---|---|---|
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | 13 | SOD1 | SOD | superoxide dismutase | |
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | 9 | APP | amyloid | |
| 6893 | MAPT | microtubule-associated protein tau | 8 | tau protein | |
| 10417 | RPS27A | ribosomal protein S27a | 4 | ubiquitin | |
| 613 | APOE | apolipoprotein E | 3 | APOE | apolipoprotein e | |
| 10940 | SLC1A2 | solute carrier family 1 (glial high affinity glutamate transporter), member 2 | 2 | EAAT2 | |
| 24624 | SIL1 | SIL1 homolog, endoplasmic reticulum chaperone (S. cerevisiae) | 1 | BAP | |
| 727 | ARTN | artemin | 1 | neurotrophic factor | |
| 1516 | CAT | catalase | 1 | catalase | |
| 1912 | CHAT | choline acetyltransferase | 1 | choline acetyltransferase | |
| 11049 | SLC6A3 | solute carrier family 6 (neurotransmitter transporter, dopamine), member 3 | 1 | dopamine transporter | |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | 1 | MAP | |
| 4638 | GSTP1 | glutathione S-transferase pi | 1 | glutathione transferase | |
Targets by SciMiner Full list
| HUGO ID | Symbol | Name | ActualStr | Score | FlankingText |
|---|---|---|---|---|---|
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.9 | in the gene for Cu/Zn Cu Zn superoxide dismutase (SOD1) SOD1 can be identified |
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | amyloid | 1.0 | These patients carry mutant genes for membrane spanning amyloid precursor protein (APP) APP |
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | APP | 0.6 | carry mutant genes for membrane spanning amyloid precursor protein (APP) APP |
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | APP | 0.6 | APP have tree isoforms ( containing 695 751 and 770 amino |
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | amyloid | 1.0 | The core of these plaques contains a distinct form of amyloid _amp_#x3b2 -protein (BAP), BAP which is 40 amino acids in |
| 24624 | SIL1 | SIL1 homolog, endoplasmic reticulum chaperone (S. cerevisiae) | BAP | 0.1 | plaques contains a distinct form of amyloid _amp_#x3b2 -protein (BAP), BAP which is 40 amino acids in length |
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | APP | 0.6 | BAP is derived by proteolysis from a much larger APP |
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | APP | 0.6 | Normally degradation of APP involves a proteolytic cleavage in the middle of the BAP |
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | APP | 0.6 | In AD the APP molecule is cut at both ends of the BAP domain |
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | amyloid | 1.0 | molecule which is toxic and accumulates in neuritic plaques as amyloid fibrils ([ Price et al . |
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | amyloid | 1.0 | However argument against the amyloid cascade toxicity in AD are cognitively normal individuals who have |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | MAP | 0.3 | of an abnormal form of normally occurring microtubule-associated protein (MAP), MAP termed tau |
| 6893 | MAPT | microtubule-associated protein tau | tau | 2.2 | abnormal form of normally occurring microtubule-associated protein (MAP), MAP termed tau |
| 6893 | MAPT | microtubule-associated protein tau | tau | 2.2 | Normal tau proteins are microtubule binding proteins predominantly axonal that stabilize the |
| 6893 | MAPT | microtubule-associated protein tau | tau | 2.2 | In normal brain tau is phosphorylated but the phosphate groups are in postmortal tissue |
| 6893 | MAPT | microtubule-associated protein tau | tau | 2.2 | In contrast tau protein in PHF is relatively resistant to postmortem dephosphorylation ([ |
| 6893 | MAPT | microtubule-associated protein tau | tau | 2.2 | In AD phosphorylation of tau on aberrant site could result in a protein that does |
| 613 | APOE | apolipoprotein E | APOE | 1.3 | be associated with the inheritance of apolipoprotein E 4 (APOE) APOE alleles |
| 613 | APOE | apolipoprotein E | APOE | 1.3 | APOE genotype and advancing aging are interacting risk factors for late |
| 6893 | MAPT | microtubule-associated protein tau | tau | 2.2 | HNE is toxic for P19 cells causing cross-linking of tau into high molecular weight substances that are conjugated with ubiquitin |
| 6893 | MAPT | microtubule-associated protein tau | tau | 2.2 | preferentially reacts with lysine residues that are prominent components of tau ( Uchida et al and are present in NFT and |
| 10940 | SLC1A2 | solute carrier family 1 (glial high affinity glutamate transporter), member 2 | EAAT2 | 1.8 | There is specific loss of the glial glutamate transporter protein EAAT2 in spinal cord of sALS cases ([ Fray et al |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 2.9 | with mutation in the gene encoding the superoxide dismutase (SOD SOD 1 protein ([ Rosen et al |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 2.9 | Most of the mutation in SOD 1 protein occur outside the active site and produce only |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 2.9 | SOD 1 is a Cu/Zn-binding Cu Zn-binding ubiquitous antioxidative enzyme that |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 2.9 | Loss of function in mutant SOD 1 proposes that motor neurons injury occurs by direct toxic |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 2.9 | Weakened affinity for copper in the mutant SOD with consequent leakage of copper which may produce competition between |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 2.9 | consequent leakage of copper which may produce competition between mutant SOD and other copper and zinc binding protein resulting in diminished |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 2.9 | mutations could cause an alteration in copper active site of SOD 1 ([ Deng et al |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 2.9 | Such changes could allow potential toxic gain of mutant SOD 1 to react with various subsidiary activities including peroxidase activity |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 2.9 | The wide active site channel of the mutant SOD 1 protein may enhance the access of peroxynitrite to the |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 2.9 | Mutant SOD 1 A4V protein aggregation and accumulation in the anterior horns_amp_#x2019 |
| 10940 | SLC1A2 | solute carrier family 1 (glial high affinity glutamate transporter), member 2 | EAAT2 | 1.8 | of HNE was cause of modification of astrocytic glutamate transporter EAAT2 and impaired glutamate transport in ALS ( Pedersen et al |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 2.9 | The relationship between the oxidative stress SOD 1 aggregation and accumulation of specific advanced glycation end products |
| 6893 | MAPT | microtubule-associated protein tau | tau protein | 1.0 | in contrast tau protein in phf is relatively resistant to postmortem dephosphorylation [ cooper et al ] . |
| 10417 | RPS27A | ribosomal protein S27a | ubiquitin | 1.0 | another important observation is accumulation of abnormal ubiquitin conjugated proteins in affected neurons suggesting dysfunction of the proteasome proteolytic system in these cells [ shringarpure et al ] . |
| 10417 | RPS27A | ribosomal protein S27a | ubiquitin | 1.0 | accumulation of abnormal ubiquitin conjugated proteins in affected neurons in ad suggests dysfunction of proteasome system while co existence of hne immunoreactivity in the same cells suggests the essential role of oxidative damage in |
| 613 | APOE | apolipoprotein E | apolipoprotein e | 1.0 | hne immunopositivity seems to be associated with the inheritance of apolipoprotein e 4 apoe alleles. |
| 10417 | RPS27A | ribosomal protein S27a | ubiquitin | 1.0 | hne is toxic for p19 cells causing cross linking of tau into high molecular weight substances that are conjugated with ubiquitin [ montine et al ] . |
| 4638 | GSTP1 | glutathione S-transferase pi | glutathione transferase | 1.0 | significant decrease of glutathione transferase activity and of other antioxidative enzymes was described in amygdala hippocampus and inferior parietal lobule in patients with ad [ lovell and markesbery 1998 ] . |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | superoxide dismutase | 1.0 | about 20% of the fals cases which are dominantly inherited are linked with mutation in the gene encoding the superoxide dismutase sod 1 protein [ rosen et al ] . |
| 1516 | CAT | catalase | catalase | 1.0 | nding ubiquitous antioxidative enzyme that catalyses the conversion of the toxic superoxide radical to hydrogen peroxide which in turn is converted to h 2 o by the action of glutathione peroxidase or catalase [ fridovich 1986 ] . |
| 727 | ARTN | artemin | neurotrophic factor | 1.0 | neurofilament proteins and neurotrophic factor tyrosine kinase receptors are proteins particularly susceptible to nitrotyrosine damage [ beckman et al ] . |
| 10417 | RPS27A | ribosomal protein S27a | ubiquitin | 1.0 | the same inclusions contain epitopes of ubiquitin and phosphorylated neurofilament protein [ shibata et al ] . |
| 1912 | CHAT | choline acetyltransferase | choline acetyltransferase | 1.0 | an in vitro study showed that hne impaires the glutamate and glucose transport and the choline acetyltransferase activity in cultured motor neurons [ pedersen et al ] . |
| 11049 | SLC6A3 | solute carrier family 6 (neurotransmitter transporter, dopamine), member 3 | dopamine transporter | 1.0 | these data suggest that hne is an important mediator of oxidative stress that alters dopamine uptake after binding to sh groups of the dopamine transporter and to na + /k + atpase. |