| Interacting proteins: P07101 and P30793 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P07101 and P30793 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P07101 and P30793 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P07101 and P30793 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P07101 and P30793 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P07101 and P30793 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P07101 and P30793 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P07101 and P30793 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P07101 and P30793 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P07101 and P30793 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P07101 and P30793 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P07101 and P30793 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P07101 and P30793 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P07101 and P30793 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P07101 and P30793 |
Pubmed |
SVM Score :0.0 |
| Decreased GCH 1 causes decreased tetrahydrobiopterin ( BH 4 ) , TH and DA in nigrostriatal ( NS ) terminal . ^^^ |
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| Interacting proteins: P07101 and P30793 |
Pubmed |
SVM Score :0.0 |
| These changes were accompanied by increased TH , GCH and NE transporter mRNAs . ^^^ |
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| Interacting proteins: P07101 and P30793 |
Pubmed |
SVM Score :0.0 |
| The assays of activities and function of TH , AADC , and GCH 1 and their potential use in ex vivo gene therapy of PD . ^^^ |
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| Interacting proteins: P07101 and P30793 |
Pubmed |
SVM Score :0.0 |
| We examined by immunohistochemistry the effect of salt loading on the expression of tyrosine hydroxylase ( TH ) , aromatic L amino acid decarboxylase ( AADC ) , and GTP cyclohydrolase 1 ( GCH ) in Purkinje cells of the mouse cerebellum . ^^^ The present findings suggest that the salt loading differentially affects the expression of TH , AADC and GCH in Purkinje cells of the mouse cerebellum . . ^^^ |
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| Interacting proteins: P07101 and P30793 |
Pubmed |
SVM Score :0.0 |
| The result indicates that the decreased dopamine level in the basal ganglia in JP is not due to decreased activity of GTP cyclohydrolase 1 , the enzyme for the biosynthesis of the tetrahydrobiopterin cofactor of tyrosine hydroxylase ( TH ) , and the enzyme activity in mononuclear blood cells could be a reliable method for differential diagnosis between JP and HPD / DRD . . ^^^ |
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| Interacting proteins: P07101 and P30793 |
Pubmed |
SVM Score :0.0 |
| Only denervated striata grafted with fibro blasts possessing both TH and GTP cyclohydrolase 1 genes displayed biochemical restoration . ^^^ These differences between fibroblasts transduced with TH alone and those additionally modified with the GTP cyclohydrolase 1 gene indicate that BH 4 is critical for biochemical restoration in a rat model of PD and that GTP cyclohydrolase 1 is sufficient for production of BH4 . . ^^^ |
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| Interacting proteins: P07101 and P30793 |
Pubmed |
SVM Score :0.0 |
| The decrease in GCH activity causes the decrease in tetrahydrobiopterin ( BH 4 ) levels , resulting in decreased tyrosine hydroxylase ( TH ) activity and finally in decreased dopamine levels in the nigrostriatal dopamine neurons . ^^^ Patients with Parkinson ' s disease had decreased GCH activity in parallel with the decreases in TH activity and dopamine in the striatum , probably as the results of cell death . . ^^^ |
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| Interacting proteins: P07101 and P30793 |
Pubmed |
SVM Score :0.0 |
| Using an immunohistochemical method involving highly specific antibodies produced in our laboratory , we found that these RN neurons were TH , GTP cyclohydrolase 1 , aromatic L amino acid decarboxylase immunoreactive , but DOPA and dopamine immunonegative . ^^^ |
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| Interacting proteins: P07101 and P30793 |
Pubmed |
SVM Score :0.0 |
| From its characteristic clinical features , decrease of tyrosine hydroxylase ( TH ) in the terminal of the nigrostriatal ( NS ) dopamine ( DA ) neuron is considered the main lesion of HPD and the decrease of neopterin as well as biopterin in the cerebrospinal fluid suggested GTP cyclohydrolase 1 ( GCH 1 ) as the responsible enzyme . ^^^ GCH 1 is the limiting enzyme for synthesizing tetrahydrobiopterin ( BH 4 ) , coenzyme transmitters for the synthesizing hydroxylases of aminergic neurotransmitters , but the affinity is the least for TH . ^^^ Studies of an autopsied case with dopa responsive dystonia , which was confirmed to have GCH 1 gene abnormalities , neuropathologically revealed no abnormalities except for a decrease in melanin pigmentation in the substantia nigra and histochemically a decrease in TH enzyme activities and its protein only in the striatum . ^^^ So it is suggested that in HPD , decrease of TH at the terminal of the NS DA neuron due to partial reduction of GCH 1 develops postural dystonia through the striatal direct projection in childhood with diurnal fluctuation depending on age and circadian variation of TH activities at the terminals . . ^^^ |
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| Interacting proteins: P07101 and P30793 |
Pubmed |
SVM Score :0.0 |
| When GCH activity is decreased to less than 20 % of the normal value , the activity of TH in the nigrostriatal dopaminergic neurons may be first decreased resulting in decreases in TH activity and dopamine level , and in the symptoms of HPD / DRD . ^^^ In Parkinson ' s disease ( PD ) , GCH , TH , and dopamine in the striatum may decrease in parallel , as the secondary effects caused by cell death . . ^^^ |
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| Interacting proteins: P07101 and P30793 |
Pubmed |
SVM Score :0.0 |
| Using the antiserum against GTP cyclohydrolase 1 ( GCH ) , first rate limiting enzyme of the biosynthesis of tetrahydrobiopterin ( BH 4 ) , the cofactor for TH , we proved that these TH only ir neurons in the wild mice and in the hTHTg mice were not stained with the antiserum against GCH . ^^^ Tyrosine hydroxylase ( TH ) only immunoreactive non catecholaminergic neurons in the brain of wild mice or the human TH transgenic mice do not contain GTP cyclohydrolase 1 . ^^^ |
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| Interacting proteins: P07101 and P30793 |
Pubmed |
SVM Score :0.0 |
| In the substantia nigra pars compacta , many phenylethanolamine N methyltransferase immunoreactive ( PNMT ir ) terminals as well as serotonin ir terminals were observed for the first time to be very closely situated to the tyrosine hydroxylase ( TH ) ir , aromatic L amino acid decarboxylase ir , and GTP cyclohydrolase 1 ( GCH ) ir dopaminergic cells [ Nagatsu , I . , Arai , R . , Sakai , M . , Yamawaki , Y . , Takeuchi , T . , Karasawa , N . and Nagatsu , T . , Neurosci . ^^^ Immunohistochemical colocalization of TH with GCH or PNMT in the somata and dendrites of TH positive neurons in the rostral ventrolateral reticular formation of the medulla oblongata ( C 1 region , [ Hokfelt , T . , Fuxe , K . , Goldstein , M . and Johansson , O . , Brain Res . , 66 ( 1974 ) 235 251 ] ) was proved by a double labeling immunofluorescence method with a confocal laser scanning microscope , indicating that the neurons are adrenergic . ^^^ |
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| Interacting proteins: P07101 and P30793 |
Pubmed |
SVM Score :0.0 |
| In adrenals , basal levels of tyrosine hydroxylase ( TH ) , dopamine beta hydroxylase ( DBH ) , phenylethanolamine N methyltransferase ( PNMT ) and GTP cyclohydrolase 1 ( GTPCH ) mRNAs were markedly elevated in FSL rats compared to the control strain . ^^^ |
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| Interacting proteins: P07101 and P30793 |
Pubmed |
SVM Score :0.0 |
| Recombinant adeno associated viruses expressing human TH or GTP cyclohydrolase 1 ( GTPCH 1 ) were injected into the striatum of DA / mice . ^^^ A virus expressing only TH was less effective , and one expressing GTPCH 1 alone was ineffective . ^^^ |
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| Interacting proteins: P07101 and P30793 |
Pubmed |
SVM Score :0.0 |
| TH activity is regulated by the concentration of the cofactor tetrahydrobiopterin ( BH 4 ) , whose level is regulated by GTP cyclohydrolase 1 ( GCH ) activity . ^^^ Thus , GCH activity indirectly regulates TH activity and catecholamine levels . 2 . ^^^ Mutations of GCH result in reductions in GCH activity , BH 4 , TH activity , and dopamine , causing either recessively inherited GCH deficiency or dominantly inherited hereditary progressive dystonia [ HPD ; Segawa ' s disease ; also called dopa responsive dystonia ( DRD ) ] . 4 . ^^^ |
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| Interacting proteins: P07101 and P30793 |
Pubmed |
SVM Score :0.0 |
| Northern blots were used to assess changes in mRNA levels for TH , DBH , and GTP cyclohydrolase 1 ( GTPCH ) in the LC in response to the stress . ^^^ |
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| Interacting proteins: P07101 and P30793 |
Pubmed |
SVM Score :0.0 |
| The intracellular concentrations of BH 4 , which are mainly determined by GCH activity , may regulate the activity of TH ( an enzyme synthesizing catecholamines from tyrosine ) , TPH ( an enzyme synthesizing serotonin and melatonin from tryptophan ) , PAH ( an enzyme required for complete degradation of phenylalanine to tyrosine , finally to CO 2 + H2O ) , and also the activity of NOS ( an enzyme forming NO from arginine ) , Dominantly inherited hereditary progressive dystonia ( HPD ) , also termed DOPA responsive dystonia ( DRD ) or Segawa ' s disease , is a dopamine deficiency in the nigrostriatal dopamine neurons , and is caused by mutations of one allele of the GCH gene . ^^^ Dopamine biosynthesis in different groups of dopamine neurons may be differentially regulated by TH activity , depending on intracellular BH 4 concentrations and GCH activity . ^^^ |
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| Interacting proteins: P07101 and P30793 |
Pubmed |
SVM Score :0.0 |
| BACKGROUND : Although mutations in the gene GCH 1 , coding for the tetrahydrobiopterin ( BH 4 ) biosynthetic enzyme guanosine triphosphate cyclohydrolase 1 , have been identified in some patients with DRD , the actual status of brain BH 4 ( the cofactor for tyrosine hydroxylase [ TH ] ) is unknown . ^^^ METHODS : The authors sequenced GCH 1 and measured levels of total biopterin ( BP ) and total neopterin ( NP ) , TH , and dopa decarboxylase ( DDC ) proteins , and the DA and vesicular monoamine transporters ( DAT , VMAT 2 ) in autopsied brain of two patients with typical DRD . ^^^ |
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| Interacting proteins: P07101 and P30793 |
Pubmed |
SVM Score :0.0 |
| Rat marrow stromal cells ( rMSCs ) and human marrow stromal cells ( hMSCs ) were genetically engineered by transduction with retroviruses encoding tyrosine hydroxylase ( TH ) and GTP cyclohydrolase 1 , the enzyme necessary for production of the tetrahydrobiopterin cofactor for TH ( BH 4 ) . ^^^ |
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| Interacting proteins: P07101 and P30793 |
Pubmed |
SVM Score :0.0 |
| GCH 1 isthe rate limiting enzyme for the biosynthesis of tetrahydrobiopterin ( BH 4 ) , the cofactor for tyrosine hydroxylase ( TH ) , which is the first and rate limiting enzyme of DA synthesis . ^^^ These findings on DRD indicate that the nigrostriatal DA neurons may be most susceptible to the decreases in GCH 1 activity , BH 4 level , TH activity , and DA level , and that DRD is the DA deficiency without neuronal death in contrast to juvenile parkinsonism or Parkinson ' s disease with DA cell death . . ^^^ |
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| Interacting proteins: P07101 and P30793 |
Pubmed |
SVM Score :0.0 |
| Guanosine triphosphate ( GTP ) cyclohydrolase 1 ( GCH ) is the first and rate limiting enzyme for biosynthesis of tetrahydrobiopterin , the cofactor of tyrosine hydroxylase ( TH ) . ^^^ The present study aims at elucidating whether GCH and TH coexist in the same neurons of the human brain with the aid of immunohistochemical dual labeling . ^^^ However , some neurons in the dorsal and dorsomedial hypothalamic nuclei are stained only for GCH or TH . ^^^ The present observation suggests that L dopa is not produced in the cells immunoreactive for TH but not for GCH , and that TH in these cells which lack GCH may have an unidentified role other than dopa synthesis . . ^^^ |
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| Interacting proteins: P07101 and P30793 |
Pubmed |
SVM Score :0.0 |
| Not only levels of TH and AADC but also levels of tetrahydrobiopterin ( BH 4 ) , a cofactor of TH , and GTP cyclohydrolase 1 ( GCH ) , a rate limiting enzymes for BH 4 biosynthesis , are reduced in parkinsonian striatum . ^^^ In the present study , we investigated whether transduction with separate AAV vectors expressing TH , AADC , and GCH was effective for gene therapy of PD . ^^^ In vitro experiments showed that triple transduction with AAV TH , AAV AADC , and AAV GCH resulted in greater dopamine production than double transduction with AAV TH and AAV AADC in 293 cells . ^^^ These results suggest that GCH , in addition to TH and AADC , is important for effective gene therapy of PD . . ^^^ |
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| Interacting proteins: P07101 and P30793 |
Pubmed |
SVM Score :0.0 |
| Among the enzymes involved in the system for catecholamine biosynthesis , GTP cyclohydrolase 1 ( GCH ) contributes to the system as the first and rate limiting enzyme for the de novo biosynthesis of tetrahydrobiopterin ( BH 4 ) , which is the cofactor for tyrosine hydroxylase ( TH ) . ^^^ After a 5 microg i . p . injection of LPS , the protein expression of GCH and TH in both nuclei was examined by immunohistochemistry . ^^^ The staining intensity of GCH positive cells increased at 6 h , whereas no significant change in the staining intensity of TH positive cells was detected . ^^^ |
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| Interacting proteins: P07101 and P30793 |
Pubmed |
SVM Score :0.0 |
| Here , we examined the possibility of using several different promoters and either a self inactivating retrovirus ( pSIR ) or standard retroviruses to introduce into marrow stromal cells ( MSCs ) , the two genes necessary for the cells to synthesize L DOPA . pSIR vectors were constructed using the mouse phosphoglycerate kinase 1 ( PGK ) promoter or the cytomegalovirus ( CMV ) promoter to drive expression of either a GFP reporter gene or a bicistronic sequence containing the genes for human tyrosine hydroxylase type 1 ( TH ) and rat GTP cyclohydrolase 1 ( GC ) separated by an internal ribosome entry site ( IRES ) . rMSCs were successfully transduced with both standard retroviral vectors and pSIR containing the PGK promoter . ^^^ |
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| Interacting proteins: P07101 and P30793 |
Pubmed |
SVM Score :0.0 |
| These are DYT 1 , encoding torsin A and mutant in the early onset generalized form , GCH 1 ( formerly known as DYT 5 ) , encoding GTP cyclohydrolase 1 and mutant in dominant dopa responsive dystonia , and TH , encoding tyrosine hydroxylase and mutant in the recessive form of the disease . ^^^ |
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| Interacting proteins: P07101 and P30793 |
Pubmed |
SVM Score :0.0 |
| METHODS : The genes for dopamine synthetic enzymes , tyrosine hydroxylase ( TH ) , aromatic L amino acid decarboxylase ( AADC ) , and GTP cyclohydrolase 1 ( GCH , an enzyme critical for tetrahydrobiopterin synthesis ) were contransduced into 293 cells with separate AAV vectors . ^^^ Expressions of TH , AADC and GCH were detected by Western blot analysis . ^^^ RESULTS : TH , AADC and GCH were effectively coexpressed in transduced cells with three separate AAV vectors , AAV TH , AAV AADC and AAV GCH . ^^^ CONCLUSION : The triple transduction of TH , AADC and GCH genes with separate AAV vectors is effective , which might be important to gene therapy for Parkinson ' s disease . . ^^^ |
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| Interacting proteins: P07101 and P30793 |
Pubmed |
SVM Score :0.0 |
| In addition to tyrosine hydroxylase ( TH ) and aromatic L amino acid decarboxylase ( AADC ) , GTP cyclohydrolase 1 ( GCH ) is necessary for efficient DA production . ^^^ Mixtures of three separate AAV vectors expressing TH , AADC , and GCH , respectively , were stereotaxically injected into the unilateral putamen of 1 methyl 4 phenyl 1 , 2 , 3 , 6 tetrahydropyridine treated monkeys . ^^^ Coexpression of the enzymes in the unilateral putamen resulted in remarkable improvement in manual dexterity on the contralateral to the AAV TH / AADC / GCH injected side . ^^^ TH immunoreactive ( TH IR ) , AADC IR , and GCH IR cells were present in a large region of the putamen . ^^^ Microdialysis demonstrated that concentrations of DA in the AAV TH / AADC / GCH injected putamen were increased compared with the control side . ^^^ |
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| Interacting proteins: P07101 and P30793 |
Pubmed |
SVM Score :0.0 |
| GTP cyclohydrolase 1 ( GCH ) is the rate limiting enzyme for the biosynthesis of tetrahydrobiopterin ( BH ( 4 ) ) , known as an essential cofactor for TH ; and here we found the increased expression of GCH in 5 1 overexpressing clones . ^^^ GTP cyclohydrolase 1 ( GCH ) is the rate limiting enzyme for the biosynthesis of tetrahydrobiopterin ( BH ( 4 ) ) , known as an essential cofactor for TH ; and here we found the increased expression of GCH in 5 1 overexpressing clones . ^^^ |
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| Interacting proteins: P07101 and P30793 |
Pubmed |
SVM Score :0.0 |
| Three enzymes are necessary for efficient dopamine synthesis : tyrosine hydroxylase ( TH ) converts tyrosine to L DOPA , aromatic L amino acid decarboxylase ( AADC ) then converts L DOPA to dopamine , and guanosine triphosphate cyclohydrolase 1 ( GCH ) is the rate limiting enzyme for the synthesis of TH co factor tetrahydrobiopterine . ^^^ We have previously demonstrated that transduction with separate adeno associated virus ( AAV ) vectors expressing TH , AADC , and GCH is effective in reducing motor abnormalities in 6 hydroxydopamine lesioned rats and in MPTP treated monkeys . ^^^ |
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| Interacting proteins: P07101 and P30793 |
Pubmed |
SVM Score :0.0 |
| However , addition of AADC to the grafts of genetically modified cells expressing tyrosine hydroxylase ( TH ) and GTP cyclohydrolase 1 ( GCH 1 ) , which produce L DOPA in parkinsonian rats , resulted in decreased production of L DOPA and dopamine owing to feedback inhibition of TH by dopamine . ^^^ Both cell types were also transduced with GCH 1 to provide the obligate TH cofactor , tetrahydrobiopterin . ^^^ |
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| Interacting proteins: P07101 and P30793 |
Pubmed |
SVM Score :0.0 |
| These data also indicate that GCH expression , which is often coordinately regulated with TH expression , can be controlled independently of TH during development . . ^^^ |
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| Interacting proteins: P07101 and P30793 |
Pubmed |
SVM Score :0.0 |
| Nicotine also elevated mRNA levels of GTP cyclohydrolase 1 ( GTPCH ) , rate limiting in biosynthesis of TH ' s essential cofactor tetrahydrobiopterin in both dopaminergic locations . ^^^ |
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| Interacting proteins: P07101 and P30793 |
Pubmed |
SVM Score :0.0 |
| Notwithstanding the discovery of GCH 1 and TH mutations in autosomal dominant and autosomal recessive DRD , respectively , a therapeutic trial with levodopa is still the most practical approach to the diagnosis of DRD . ^^^ |
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| Interacting proteins: P07101 and P30793 |
Pubmed |
SVM Score :0.0 |
| A self inactivating EIAV minimal lentiviral vector that expresses tyrosine hydroxylase ( TH ) , aromatic amino acid dopa decarboxylase ( AADC ) , and GTP cyclohydrolase 1 ( CH 1 ) in a single transcription unit has been generated . ^^^ |
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| Interacting proteins: P07101 and P30793 |
Pubmed |
SVM Score :0.0 |
| Dopamine production can be restored to specific brain regions by using adeno associated viruses expressing TH and GTP cyclohydrolase 1 ( GTPCH 1 ) . ^^^ |
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| Interacting proteins: P07101 and P30793 |
Pubmed |
SVM Score :0.0 |
| Behavioral correction of Parkinsonian rats following the transplantation of immortalized fibroblasts genetically modified with TH and GCH genes . ^^^ Eukaryotic plasmid vectors encoding the tyrosine hydroxylase ( TH ) gene and GTP cyclohydrolase 1 ( GCH ) gene were constructed and introduced into immortalized fibroblasts obtained from SV 40 large antigen ( LT ( AG ) ) transformed rat primary fibroblasts . ^^^ TH and GCH positive clones were selected and identified by immunohistochemistry and RT PCR , respectively . ^^^ Hemi parkinsonian rats created using 6 hydroxydopamine ( 6 OHDA ) were used to assess the therapeutic effect created by the co implantation of immortalized fibroblasts genetically modified by TH or GCH genes . ^^^ This work demonstrates that the co transplantation of immortalized fibroblasts genetically modified by TH and GCH genes may be developed as a valuable approach to the treatment of Parkinson ' s disease . . ^^^ |
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| Interacting proteins: P07101 and P30793 |
Pubmed |
SVM Score :0.0 |
| Dopa responsive dystonia is a heterogeneous group with several causes ( GCH 1 mutations , compound mutations in GCH 1 , mutations in TH gene , or in 6 PTS gene ) . ^^^ |
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| Interacting proteins: P07101 and P30793 |
Pubmed |
SVM Score :0.0 |
| To investigate the possibility of using ES cells as a carrier of therapeutic gene ( s ) , human ES cells ( MB 03 ) were co transfected with cDNAs coding for tyrosine hydroxylase ( TH ) and GTP cyclohydrolase 1 ( GTPCH 1 ) , then bulk selected in the presence of neomycin and hygromycin B . ^^^ |
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| Interacting proteins: P07101 and P30793 |
Pubmed |
SVM Score :0.0 |
| Recessively inherited deficiency of TH was recently identified and incorporated into recent concepts of genetic dystonias as the cause of recessive Dopa responsive dystonia or Segawa ' s syndrome in analogy to dominantly inherited GTP cyclohydrolase 1 deficiency . ^^^ We report four patients with TH deficiency and two with GTP cyclohydrolase 1 deficiency . ^^^ Compared with patients with dominantly inherited GTP cyclohydrolase 1 deficiency , catecholaminergic neurotransmission is severely and constantly impaired in TH deficiency . ^^^ |
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| Interacting proteins: P07101 and P30793 |
Pubmed |
SVM Score :0.0 |
| We determined changes in mRNA levels of tyrosine hydroxylase ( TH ) , rate limiting enzyme in catecholamine ( CA ) biosynthesis of GTP cyclohydrolase 1 ( GTPCH ) , rate limiting enzyme in biosynthesis as well as of tetrahydrobiopterin ( BH 4 ) , and concentration of BH 4 , which is an essential cofactor for TH , tryptophan hydroxylase and nitric oxide synthase . ^^^ |
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| Interacting proteins: P07101 and P30793 |
Pubmed |
SVM Score :0.0 |
| METHODS : Cos 7 cells were transfected with separate adeno associated virus ( AAV ) expressing tyrosine hydroxylase ( TH ) gene , aromatic L amino acid decarboxylase ( AADC ) gene and GTP cyclohydrolase 1 ( GCH 1 ) gene . ^^^ When Cos 7 cells expressing TH , AADC and GCH 1 were cocultured , they produced large amount of dopamine in the condition of existance of L tyrosine . ^^^ |
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| Interacting proteins: P07101 and P30793 |
Pubmed |
SVM Score :0.0 |
| The pathophysiology of Segawa disease is that partial deficiency of BH 4 resulted from GCH 1 deficiency , rate limiting enzyme of synthesis of BH 4 , affects the TH activity at terminal of nigrostriatal dopamine neuron . ^^^ |
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| Interacting proteins: P07101 and P30793 |
Pubmed |
SVM Score :0.0 |
| In this study we used 33 rats with severe nigrostriatal dopamine depletion and showed that in vivo gene transfer of the DA synthetic enzymes tyrosine hydroxylase ( TH ) and GTP cyclohydrolase 1 ( GCH 1 ) using recombinant adeno associated virus vectors can provide a constant source of DOPA production locally in the striatum , at a level that is effective in reducing L DOPA induced dyskinesias by > 85 % , and reverse lesion induced motor impairments . ^^^ Furthermore , the abnormal expression of DeltaFosB , prodynorphin and preproenkephalin mRNA within the striatal projection neurons normally seen in dyskinetic animals was completely reversed by TH GCH 1 gene transfer . ^^^ |
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| Interacting proteins: P07101 and P30793 |
Pubmed |
SVM Score :0.0 |
| The central hypothesis of this study is that coexpression of four dopamine biosynthetic and transporter genes in striatal neurons can support the efficient production and regulated , vesicular release of dopamine : tyrosine hydroxylase ( TH ) converts tyrosine to L 3 , 4 dihydroxyphenylalanine ( L DOPA ) , GTP cyclohydrolase 1 ( GTP CH 1 ) is the rate limiting enzyme in the biosynthesis of the cofactor for TH , aromatic amino acid decarboxylase ( AADC ) converts L DOPA to dopamine , and a vesicular monoamine transporter ( VMAT 2 ) transports dopamine into synaptic vesicles , thereby supporting regulated , vesicular release of dopamine and relieving feedback inhibition of TH by dopamine . ^^^ Helper virus free herpes simplex virus type 1 vectors that coexpress the three dopamine biosynthetic enzymes ( TH , GTP CH 1 , and AADC ; 3 gene vector ) or these three dopamine biosynthetic enzymes and the vesicular monoamine transporter ( TH , GTP CH 1 , AADC , and VMAT 2 ; 4 gene vector ) were compared . ^^^ |
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| Interacting proteins: P07101 and P30793 |
Pubmed |
SVM Score :0.0 |
| To examine if genetically modified NSCs are a suitable source for the cell and gene therapy of PD , an immortalized mouse NSC line , C17 . 2 , was transduced with tyrosine hydroxylase ( TH ) gene and with GTP cyclohydrolase 1 ( GTPCH 1 ) gene , which are important enzymes in dopamine biosynthesis . ^^^ The expression of TH in transduced C17 . 2 THGC cells was confirmed by RT PCR , Western blot analysis , and immunocytochemistry , and expression of GTPCH 1 by RT PCR . ^^^ The level of L DOPA released by C17 . 2 THGC cells , as determined by HPLC assay , was 3793 pmol / 10 ( 6 ) cells , which is 760 fold higher than that produced by C17 . 2 TH cells , indicating that GTPCH 1 expression is important for L DOPA production by transduced C17 . 2 cells . ^^^ |
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| Interacting proteins: P07101 and P30793 |
Pubmed |
SVM Score :0.0 |
| These results indicate that long term GDNF delivery is a major factor affecting dopamine biosynthesis via a direct or indirect modulation of TH and GTPCH 1 and further underscore the importance of assessing both GDNF dose and delivery duration prior to clinical application in order to circumvent potentially adverse pharmacological effects on the biosynthesis of dopamine . . ^^^ |
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| Interacting proteins: P07101 and P30793 |
Pubmed |
SVM Score :0.0 |
| These data suggest that the Ras MEK pathway is required for coordinate expression of the GCH and TH genes induced by neurotrophins . . ^^^ |
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| Interacting proteins: P07101 and P30793 |
Pubmed |
SVM Score :0.0 |
| There are at least three causative genes for DRD : ( 1 ) the GCH 1 gene on chromosome 14q22 . 1 q22 . 2 , which encodes GTP cyclohydrolase 1 ( GTPCH ) , the first enzyme in the biosynthetic pathway for tetrahydrobiopterin ( BH 4 ; the essential cofactor for tyrosine hydroxylase [ THI ] ) , ( 2 ) the TH gene on 11 p15 . 5 , coding for the enzyme TH that catalyzes the rate limiting step in the catecholamine biosynthesis , and ( 3 ) an as yet undefined gene on 14q13 ( DYT 14 ) . ^^^ In our series , after conducting additional GCH 1 testing ( Southern blotting , cDNA sequencing , etc . ) and TH analysis , 86 % of families with DRD or dystonia with motor delay ( an intermediate phenotype between GTPCH deficient DRD [ mild ] and GTPCH deficient hyperphenylalaninemia [ severe ] ) had identifiable GCH 1 or ( rarely ) TH mutations . ^^^ The extent of striatal TH protein loss may be critical in determining DRD symptomatology and could contribute to gender related incomplete penetrance of GCH 1 mutations in GTPCH deficient DRD families . ^^^ |
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| Interacting proteins: P07101 and P30793 |
Pubmed |
SVM Score :0.0 |
| Analysis of the GTP cyclohydrolase 1 gene ( GCH 1 ) and the tyrosine hydroxylase gene ( TH ) , mutated in dopa responsive dystonia and juvenile PD , have also been included . ^^^ No other putative disease causing TH or GCH 1 mutations were found . ^^^ In conclusion , homozygous , or compound heterozygous PARK 2 mutations , and mutations in GCH 1 and TH , are rare even in a population of PD patients with early onset of the disease . . ^^^ |
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| Interacting proteins: P07101 and P30793 |
Pubmed |
SVM Score :0.0 |
| Next , we co transduced the F 3 NSC line with genes encoding tyrosine hydroxylase ( TH ) and GTP cyclohydrolase 1 ( GTPCH 1 ) in order to generate dopamine producing NSC . ^^^ These results indicate that human NSC , genetically transduced with TH and GTPCH 1 genes , have great potential in clinical utility for cell replacement therapy in patients suffering from Parkinson disease . . ^^^ |
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| Interacting proteins: P07101 and P30793 |
Pubmed |
SVM Score :0.0 |
| GDNF stimulation of primary dopaminergic neurones expressing both tyrosine 3 monooxygenase and GTPCH 1 resulted in a dose dependent doubling of GTPCH 1 activity , and a concomitant increase in tetrahydrobiopterin levels whereas tyrosine 3 monooxygenase activity was not altered . ^^^ |
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