We investigated TH polymorphism in 44 patients with sporadic PD, 48 patients with familial PD and 89 of their unaffected relatives, and 50 control subjects.
Our results indicate that to analyze the relationship between dopa-responsive dystonia-related genes and PD, it is important to screen GCH1 and test rs6356 of TH in a larger sample.
Paraquat (PQ) and maneb (MB) are able to induce neurotoxic effects by promoting α-synuclein (α-syn) aggregates and altering tyrosine hydroxylase (TH), thus increasing the risk of Parkinson's disease (PD).
In this review, we have summarized the latest evidence on TH genetic variants in PD, including our ongoing effort of using whole exome sequencing to search for rare variants in PD patients.
Bovine papilloma virus type-1 (BPV-1)-based expression plasmids TkBPVTH and CGalBPVTH encoding the rat tyrosine hydroxylase (TH) enzyme have been designed for the development of gene therapy for experimental Parkinson's disease.
Intravenous glial-derived neurotrophic factor gene therapy of experimental Parkinson's disease with Trojan horse liposomes and a tyrosine hydroxylase promoter.
Following the establishment of a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) model, AQP4-deficient (AQP4<sup>-/-</sup> ) mice displayed significantly stronger microglial inflammatory responses and remarkably greater losses of tyrosine hydroxylase (TH<sup>+</sup> )-positive neurons than did wild-type AQP4 (AQP4<sup>+/+</sup> ) controls.
Because activation of the innate cellular immune response, mediated by microglia, has been linked to the neurodegeneration in PD, in the present study, we evaluated the effects of lipopolysaccharide (LPS) and 6-hydroxydopamine (6-OHDA) on microglia's morphology, reflective of their activity, as well as tyrosine hydroxylase (TH)-positive neurons in SNpc and motor behavior.
Our data show that scavenging intracellular or mitochondrial ROS inhibits the microglial activation and lipid peroxidation, while protecting the tyrosine hydroxylase (TH) in the striata of PD model mice.
Moreover, immunohistochemistry for tyrosine hydroxylase (TH) revealed a significant reduction in the number of DAergic neurons in the substantia nigra of PD mice following BCCAS, particularly in the PDMCI + BCCAS group.
Tyrosine hydroxylase (TH) was increased significantly and <i>α</i>-synuclein protein expression was reduced in the EX-PD group compared to the SED-PD group.
In addition, through cultured primary mesencephalic neuron-glia cell experiments, we illustrate that Lico.A attenuates the decrease in [³H] dopamine (DA) uptake and the loss of tyrosine hydroxylase-immunoreactive (TH-ir) neurons in LPS-induced PD models in vitro.
<i>In vivo</i> results demonstrated that oral administration of NTZ (50 mg/kg) in an acute MPTP mouse model of PD conferred significant protection against the loss of tyrosine hydroxylase (TH)-positive neurons of substantia nigra.
Parkinson's disease is an obvious target for the development of gene therapy procedures which could involve both the delivery of the gene encoding tyrosine hydroxylase to boost dopamine production or the delivery of genes encoding neurotrophic factors such as GDNF to promote the survival of dopaminergic neurons.
In a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of PD, 17e significantly attenuated loss of tyrosine hydroxylase-immunopositive dopaminergic neurons, suppressed microglial activation, and alleviated PD-associated motor dysfunction.
Finally, upregulation of miR-190 inhibited the activation of microglial cells and inflammation and attenuated the tyrosine hydroxylase loss in SNpc in MPTP-induced PD mice.
This review discusses the historical overview of TH, BH4-, and other CA-related enzymes and their genes in relation to the pathophysiology of PD, the development of drugs, such as L-DOPA, and future prospects for drug and gene therapy for PD, especially the potential of induced pluripotent stem (iPS) cells.
Brain transplantation of human neural stem cells transduced with tyrosine hydroxylase and GTP cyclohydrolase 1 provides functional improvement in animal models of Parkinson disease.
Further study of the 6-OHDA-induced PD rat model indicated that FGF18 improved the behavioral dysfunction in PD rats and reduced the tyrosine hydroxylase (TH)-positive neuronal loss in the SN.
Also, immunohistochemical data using a tyrosine hydroxylase antibody and cresyl violet staining demonstrated that Tat-SAG obviously protected DA neurons in the SN against MPTP toxicity in a PD mouse model.