)| PMID |
10742195 ( ) |
|---|---|
| Title | Metals and neuroscience. |
| Abstract | Data are now rapidly accumulating to show that metallochemical reactions might be the common denominator underlying Alzheimer's disease, amyotrophic lateral sclerosis, prion diseases, cataracts, mitochondrial disorders and Parkinson's disease. In these disorders, an abnormal reaction between a protein and a redox-active metal ion (copper or iron) promotes the formation of reactive oxygen species or radicalization. It is especially intriguing how the powerful catalytic redox activity of antioxidant Cu/Zn-superoxide dismutase can convert into a pro-oxidant activity, a theme echoed in the recent proposal that Abeta and PrP, the proteins respectively involved in Alzheimer's disease and prion diseases, possess similar redox activities. General Hospital East, Charlestown, MA 02129, USA. bush@helix.mgh.harvard.edu |
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)) | 38 | SOD-like | SOD1 | superoxide dismutase | |
| 1325 | C4BPA | complement component 4 binding protein, alpha | 16 | PrP | |
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | 7 | APP | amyloid | |
| 1613 | CCS | copper chaperone for superoxide dismutase | 6 | CCS | |
| 11180 | SOD2 | superoxide dismutase 2, mitochondrial | 4 | SOD2 | |
| 613 | APOE | apolipoprotein E | 3 | apolipoprotein e | apoE | |
| 12442 | TYR | tyrosinase (oculocutaneous albinism IA) | 2 | tyrosinase | |
| 11014 | SLC30A3 | solute carrier family 30 (zinc transporter), member 3 | 2 | ZnT3 | |
| 3951 | FXN | frataxin | 2 | frataxin | |
| 11138 | SNCA | synuclein, alpha (non A4 component of amyloid precursor) | 2 | alpha synuclein | |
| 9509 | PSEN2 | presenilin 2 (Alzheimer disease 4) | 1 | presenilin 2 | |
| 2295 | CP | ceruloplasmin (ferroxidase) | 1 | ceruloplasmin | |
| 412 | ALDH9A1 | aldehyde dehydrogenase 9 family, member A1 | 1 | aldehyde dehydrogenase | |
| 118 | ACO2 | aconitase 2, mitochondrial | 1 | aconitase | |
| 798 | ATOX1 | ATX1 antioxidant protein 1 homolog (yeast) | 1 | Atx1 | |
| 31395 | COX8B | cytochrome c oxidase, subunit 8B pseudogene | 1 | cytochrome c oxidase | |
| 1504 | CASP3 | caspase 3, apoptosis-related cysteine peptidase | 1 | caspase 3 | |
| 9508 | PSEN1 | presenilin 1 (Alzheimer disease 3) | 1 | presenilin 1 | |
| 6893 | MAPT | microtubule-associated protein tau | 1 | tau | |
| 9655 | PTPN3 | protein tyrosine phosphatase, non-receptor type 3 | 1 | tyrosine phosphatase | |
Targets by SciMiner Full list
| HUGO ID | Symbol | Name | ActualStr | Score | FlankingText |
|---|---|---|---|---|---|
| 1325 | C4BPA | complement component 4 binding protein, alpha | PrP | 1.9 | a theme echoed in the recent proposal that A_amp_#x3b2 and PrP the proteins respectively involved in Alzheimer_amp_#x2019 s disease and prion |
| 11014 | SLC30A3 | solute carrier family 30 (zinc transporter), member 3 | ZnT3 | 1.0 | have cloned and characterized in the past five years is ZnT3 whose protein resides on synaptic vesicle membranes of zinc-containing neurons |
| 11014 | SLC30A3 | solute carrier family 30 (zinc transporter), member 3 | ZnT3 | 1.0 | The phenotype of ZnT3 knockout mice was recently reported by this group 7 |
| 1613 | CCS | copper chaperone for superoxide dismutase | CCS | 0.9 | the elaboration of the copper chaperone of superoxide dismutase (CCS) CCS |
| 1613 | CCS | copper chaperone for superoxide dismutase | CCS | 0.9 | Recently CCS was reported to play an essential role in loading Cu |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 1.4 | essential role in loading Cu 2 onto superoxide dismutase (SOD)1 SOD 1 under conditions of low cytosolic Cu 2 8 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.9 | it shows that the cell possesses machinery to ensure that SOD1 antioxidant activity (which which depends upon a Cu 2 catalytic |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.9 | It is proposed that although SOD1 has a very high affinity (femtomolar) femtomolar Cu 2 -binding |
| 1613 | CCS | copper chaperone for superoxide dismutase | CCS | 0.9 | (femtomolar) femtomolar Cu 2 -binding site and does not require CCS to be loaded with Cu 2 when Cu 2 is |
| 1613 | CCS | copper chaperone for superoxide dismutase | CCS | 0.9 | so low (less less than one atom per cell that CCS facilitates Cu 2 loading onto SOD1 by competing against the |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.9 | atom per cell that CCS facilitates Cu 2 loading onto SOD1 by competing against the pool of cytosolic Cu 2 scavengers |
| 1613 | CCS | copper chaperone for superoxide dismutase | CCS | 0.9 | The crystal structure of CCS reveals a dimeric protein with one domain resembling the metallochaperone |
| 798 | ATOX1 | ATX1 antioxidant protein 1 homolog (yeast) | Atx1 | 2.1 | a dimeric protein with one domain resembling the metallochaperone protein Atx1 and a second domain resembling SOD1 itself but lacking its |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.9 | resembling the metallochaperone protein Atx1 and a second domain resembling SOD1 itself but lacking its metal-binding sites and catalytic-site residues 9 |
| 1613 | CCS | copper chaperone for superoxide dismutase | CCS | 0.9 | The work on CCS the Cu 2 ATPases and MT underscores the understanding that |
| 12442 | TYR | tyrosinase (oculocutaneous albinism IA) | tyrosinase | 1.0 | function of numerous enzymes of interest to neurobiology such as tyrosinase ceruloplasmin cytochrome c oxidase and dopamine _amp_#x3b2 hydroxylase free or |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.9 | unlikely to play any role in disease biochemistry outside of SOD1 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.9 | Familial amyotrophic lateral sclerosis SOD1 and copper |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 1.4 | the elucidation of how a mutation of Cu/Zn Cu Zn SOD (SOD1) SOD1 engenders a gain of function that changes this |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.9 | of how a mutation of Cu/Zn Cu Zn SOD (SOD1) SOD1 engenders a gain of function that changes this ubiquitous antioxidant |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.9 | abundant literature on the oxidative insult caused by the FALS-linked SOD1 mutation 15 and 16 as well as the formation of |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.9 | mutation 15 and 16 as well as the formation of SOD1 aggregates in affected motor neurons and glia 17 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.9 | I believe will become fundamental not only to understanding how SOD1 mutations cause FALS but also how well known toxic proteins |
| 1325 | C4BPA | complement component 4 binding protein, alpha | PrP | 1.9 | also how well known toxic proteins such as A_amp_#x3b2 and PrP could function as antioxidants (see see below |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 1.4 | Alone it has a SOD activity with a rate constant the same as SOD1 itself |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.9 | a SOD activity with a rate constant the same as SOD1 itself 18 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.9 | The purpose of the SOD1 protein is to harness this activity of Cu 2 without |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.9 | Hence the Cu 2 at the active site of SOD1 has the potential to be abnormally redox reactive generating unwanted |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.9 | 19 describing a likely mechanism for the pathogenicity of mutant SOD1 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.9 | The pathogenic SOD1 mutations do not cause a loss of function when the |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 1.4 | al 19 observed that altered Cu 2 coordination made Zn-deficient SOD (wild wild type or mutant a more efficient oxidant able |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 1.4 | The altered reactivity of Zn-deficient SOD enables it to be reduced by cellular reductants (such such |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 1.4 | SOD then donates an electron to O 2 to generate O |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.9 | Thus if SOD1 loses Zn 2 its catalytic activity is diminished while it |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.9 | The O 2 _amp_#x2212 formed by Zn-deficient SOD1 might not be released as a free intermediate which would |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.9 | released as a free intermediate which would explain why excess SOD1 fails to slow disease progression in FALS/SOD1 FALS SOD1 transgenic |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.9 | excess SOD1 fails to slow disease progression in FALS/SOD1 FALS SOD1 transgenic mice 17 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.9 | Intriguingly Estevez et al 19 found that apo SOD1 was not neurotoxic in cell culture whereas Zn-deficient Cu-loaded SOD1 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.9 | SOD1 was not neurotoxic in cell culture whereas Zn-deficient Cu-loaded SOD1 was neurotoxic an effect that could be rescued by treatment |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.9 | the treatment efficacy of Cu 2 chelators upon FALS/SOD1 FALS SOD1 transgenic mice 22 |
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | amyloid | 1.0 | Familial AD-linked mutations of amyloid precursor protein (APP), APP presenilin-1 and presenilin-2 increase both cerebral |
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | APP | 0.3 | Familial AD-linked mutations of amyloid precursor protein (APP), APP presenilin-1 and presenilin-2 increase both cerebral A_amp_#x3b2 burden and A_amp_#x3b2 |
| 6893 | MAPT | microtubule-associated protein tau | tau | 0.3 | many of the other neuropathological features of AD including intraneuronal tau abnormalities and neuronal loss 23 as well as signs of |
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | amyloid | 1.0 | minor free soluble species in biological fluids is enriched in amyloid deposits |
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | amyloid | 1.0 | perhaps explaining why these animals do not form cerebral A_amp_#x3b2 amyloid |
| 613 | APOE | apolipoprotein E | apoE | 1.3 | We have also reported 25 that apolipoprotein E (apoE) apoE modulates the precipitation of A_amp_#x3b2 by Cu 2 and Zn |
| 613 | APOE | apolipoprotein E | apoE | 1.3 | by Cu 2 and Zn 2 which is important because apoE isoforms segregate with the genetic risk for AD inheritance of |
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | amyloid | 1.0 | Zn 2 in A_amp_#x3b2 amyloid deposits has recently been detected by histological fluorescent techniques in |
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | amyloid | 1.0 | that we have found on human A_amp_#x3b2 extracted from AD amyloid |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD-like | 1.4 | cell-culture data indicate that Cu/Zn-loaded Cu Zn-loaded A_amp_#x3b2 possesses catalytic SOD-like activity and that A_amp_#x3b2 1-42 has greater activity than A_amp_#x3b2 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.9 | be mechanistically related to the oxidative stress induced by mutant SOD1 |
| 1325 | C4BPA | complement component 4 binding protein, alpha | PrP | 1.9 | The infectious particle is a protein PrP Sc that collects in the CJD-affected brain and is a |
| 1325 | C4BPA | complement component 4 binding protein, alpha | PrP | 1.9 | is a modified and protease-resistant form of a ubiquitous protein PrP c |
| 1325 | C4BPA | complement component 4 binding protein, alpha | PrP | 1.9 | was the publication by David Brown et al 35 that PrP c possesses SOD activity |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 1.4 | by David Brown et al 35 that PrP c possesses SOD activity |
| 1325 | C4BPA | complement component 4 binding protein, alpha | PrP | 1.9 | of the earlier work of Brown (and and others characterizing PrP c as a Cu 2 -binding protein exhibiting high-affinity cooperative |
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | APP | 0.3 | Therefore it is especially intriguing that APP the A_amp_#x3b2 precursor which has second Cu 2 -binding and |
| 1325 | C4BPA | complement component 4 binding protein, alpha | PrP | 1.9 | out of cells 40 an activity resembling that proposed for PrP c |
| 1325 | C4BPA | complement component 4 binding protein, alpha | PrP | 1.9 | Unlike PrP c interaction with Cu 2 37 the A_amp_#x3b2 precursor interaction |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 1.4 | The SOD activity of PrP c is also intriguing because of the |
| 1325 | C4BPA | complement component 4 binding protein, alpha | PrP | 1.9 | The SOD activity of PrP c is also intriguing because of the neuropathological similarities between |
| 1325 | C4BPA | complement component 4 binding protein, alpha | PrP | 1.9 | Assuming that PrP c and A_amp_#x3b2 are indeed also physiological SOD-type antioxidants then |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.9 | Like mutant SOD1 PrP sc might be a modification of PrP that induces |
| 1325 | C4BPA | complement component 4 binding protein, alpha | PrP | 1.9 | Like mutant SOD1 PrP sc might be a modification of PrP that induces a |
| 1325 | C4BPA | complement component 4 binding protein, alpha | PrP | 1.9 | Like mutant SOD1 PrP sc might be a modification of PrP that induces a Cu 2 -related gain of function perhaps |
| 1325 | C4BPA | complement component 4 binding protein, alpha | PrP | 1.9 | supported by recent reports that Cu 2 treatment of denatured PrP Sc restores protease resistance and infectivity 42 |
| 1325 | C4BPA | complement component 4 binding protein, alpha | PrP | 1.9 | Also the respective conformations of strain variants of PrP Sc have now been reported to depend upon Cu 2 |
| 1325 | C4BPA | complement component 4 binding protein, alpha | PrP | 1.9 | Recently we have reported 44 that the copper-binding domain of PrP c reduces Cu 2 and uses O 2 to produce |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.9 | In normal SOD1 Cu A_amp_#x3b2 or PrP c the Cu 2 active site |
| 1325 | C4BPA | complement component 4 binding protein, alpha | PrP | 1.9 | In normal SOD1 Cu A_amp_#x3b2 or PrP c the Cu 2 active site would be shielded from |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 1.4 | A manganese SOD SOD2 is the mitochondrial equivalent of SOD1 preventing O 2 |
| 11180 | SOD2 | superoxide dismutase 2, mitochondrial | SOD2 | 0.9 | A manganese SOD SOD2 is the mitochondrial equivalent of SOD1 preventing O 2 _amp_#x2212 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.9 | A manganese SOD SOD2 is the mitochondrial equivalent of SOD1 preventing O 2 _amp_#x2212 from reacting with sensitive substrates such |
| 118 | ACO2 | aconitase 2, mitochondrial | aconitase | 1.3 | O 2 _amp_#x2212 from reacting with sensitive substrates such as aconitase |
| 11180 | SOD2 | superoxide dismutase 2, mitochondrial | SOD2 | 0.9 | Knockout mice for SOD2 die within the first week of life from heart failure |
| 11180 | SOD2 | superoxide dismutase 2, mitochondrial | SOD2 | 0.9 | the heart failure and subsequent early neonatal death of the SOD2 knockout mice the ROS produced within the developing brain reach |
| 11180 | SOD2 | superoxide dismutase 2, mitochondrial | SOD2 | 0.9 | By two weeks the SOD2 mutant mice develop a profound spongiform encephalopathy accompanied by gliosis |
| 9655 | PTPN3 | protein tyrosine phosphatase, non-receptor type 3 | tyrosine phosphatase | 1.0 | enzymes: caspase 3 critical for initiating apoptosis was inhibited by zn 2+ with an ic 50 _amp_#x3c; 10 nm 1:1 stoichiometry ; and the ic 50 for fructose 1 6 diphosphatase aldehyde dehydrogenase and tyrosine phosphatase were 100_amp_#x2013;200 nm. |
| 1504 | CASP3 | caspase 3, apoptosis-related cysteine peptidase | caspase 3 | 1.0 | vallee_amp_#x2019;s group [ 3 ] has now shown that nanomolar levels of zn 2+ modulated by mt regulate the activities of metabolically critical enzymes: caspase 3 critical for initiating apoptosis was inhibited by zn 2+ with an ic 50 _amp_#x3c; 10 nm 1:1 stoichiometry ; and the ic 50 for fructose 1 6 diphosphatase aldehyde dehydrogenase and tyrosine phosphatas |
| 412 | ALDH9A1 | aldehyde dehydrogenase 9 family, member A1 | aldehyde dehydrogenase | 1.0 | s of metabolically critical enzymes: caspase 3 critical for initiating apoptosis was inhibited by zn 2+ with an ic 50 _amp_#x3c; 10 nm 1:1 stoichiometry ; and the ic 50 for fructose 1 6 diphosphatase aldehyde dehydrogenase and tyrosine phosphatase were 100_amp_#x2013;200 nm. |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | superoxide dismutase | 1.0 | the most important recent contribution to understanding basic neuronal cu 2+ metabolism has been the elaboration of the copper chaperone of superoxide dismutase ccs . |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | superoxide dismutase | 1.0 | recently ccs was reported to play an essential role in loading cu 2+ onto superoxide dismutase sod 1 under conditions of low cytosolic cu 2+ [ 8 ]. |
| 2295 | CP | ceruloplasmin (ferroxidase) | ceruloplasmin | 1.0 | although cu 2+ is essential for life and the function of numerous enzymes of interest to neurobiology such as tyrosinase ceruloplasmin cytochrome c oxidase and dopamine _amp_#x3b2; hydroxylase free or incorrectly bound cu 2+ can also catalyze the generation of the most damaging radicals such as the hydroxyl radical oh _amp_#x2022; [ |
| 12442 | TYR | tyrosinase (oculocutaneous albinism IA) | tyrosinase | 1.0 | although cu 2+ is essential for life and the function of numerous enzymes of interest to neurobiology such as tyrosinase ceruloplasmin cytochrome c oxidase and dopamine _amp_#x3b2; hydroxylase free or incorrectly bound cu 2+ can also catalyze the generation of the most damaging radicals such as the hydroxyl radical oh |
| 31395 | COX8B | cytochrome c oxidase, subunit 8B pseudogene | cytochrome c oxidase | 1.0 | although cu 2+ is essential for life and the function of numerous enzymes of interest to neurobiology such as tyrosinase ceruloplasmin cytochrome c oxidase and dopamine _amp_#x3b2; hydroxylase free or incorrectly bound cu 2+ can also catalyze the generation of the most damaging radicals such as the hydroxyl radical oh _amp_#x2022; [ 10 ]. |
| 9508 | PSEN1 | presenilin 1 (Alzheimer disease 3) | presenilin 1 | 1.0 | familial ad linked mutations of amyloid precursor protein app presenilin 1 and presenilin 2 increase both cerebral a_amp_#x3b2; burden and a_amp_#x3b2;1 42 production underscoring the role that a_amp_#x3b2; metabolism plays in ad pathogenesis see [ 10 ] . |
| 9509 | PSEN2 | presenilin 2 (Alzheimer disease 4) | presenilin 2 | 1.0 | familial ad linked mutations of amyloid precursor protein app presenilin 1 and presenilin 2 increase both cerebral a_amp_#x3b2; burden and a_amp_#x3b2;1 42 production underscoring the role that a_amp_#x3b2; metabolism plays in ad pathogenesis see [ 10 ] . |
| 613 | APOE | apolipoprotein E | apolipoprotein e | 1.0 | we have also reported [ 25 ] that apolipoprotein e apoe modulates the precipitation of a_amp_#x3b2; by cu 2+ and zn 2+ which is important because apoe isoforms segregate with the genetic risk for ad; inheritance of the apoe4 isoform carries the great |
| 11138 | SNCA | synuclein, alpha (non A4 component of amyloid precursor) | alpha synuclein | 1.0 | in familial pd a mutation of the alpha synuclein gene has been identified which is important because alpha synuclein is a component of lewy bodies which typify the neuropathology. |
| 11138 | SNCA | synuclein, alpha (non A4 component of amyloid precursor) | alpha synuclein | 1.0 | one recent report [ 49 ] proposes abnormal interaction of alpha synuclein with cu 2+ in the formation of lewy bodies but the concentrations of cu 2+ used in the study were far in excess of what is likely in the tissue. |
| 3951 | FXN | frataxin | frataxin | 1.0 | friedrich_amp_#x2019;s ataxia fa is a disease characterized by neurodegeneration and cardiomyopathy and is caused by a mutation of frataxin a mitochondrial protein involved in iron homeostasis and respiratory function. |
| 3951 | FXN | frataxin | frataxin | 1.0 | frataxin has recently been shown to export non heme bound iron from the mitochondria hence the mutation appears to cause a loss of function that raises iron levels in the mitochondria [ 50 ]. |