81 results about "Tyrosine hydroxylase" patented technology

The present disclosure is directed to improved methods for efficiently producing neuroprogenitor cells and differentiated neural cells such as dopaminergic neurons and serotonergic neurons from pluripotent stem cells, for example human embryonic stem cells. Using the disclosed methods, cell populations containing a high proportion of cells positive for tyrosine hydroxylase, a specific marker for dopaminergic neurons, have been isolated. The neuroprogenitor cells and terminally differentiated cells of the present disclosure can be generated in large quantities, and therefore may serve as an excellent source for cell replacement therapy in neurological disorders such as Parkinson's disease.

A cell system for treating neurodegenerative disorders in a mammal is provided. The cell system includes a population of neurons differentiated from umbilical mesenchymal stem cells for expressing at least one of tyrosine hydroxylase (TH), dopamine-β-hydroxylase (DBH), glutamate decarboxylase (GAD), aromatic L-amino acid decarboxylase (AADC) and dopaminergic transporter (DAT) in a cell culture. A method for treating neurodegenerative disorders in a mammal is also provided. The method comprises the steps of differentiating umbilical mesenchymal stem cells into a population of neurons that express at least one of TH, DBH, GAD, AADC and DAT in a cell culture, and transplanting the population of neurons into the brain of the mammal.

Current sources of neural stem and progenitor cells for neural transplantation are essentially inaccessible in living animals. This invention relates to neural precursor cells (stem cells, progenitor cells or a combination of both types of cells) isolated from the olfactory epithelium of mammals that can be passaged and expanded, and that will differentiate into cell types of the central nervous system (CNS), including astrocytes, oligodendrocytes, and tyrosine-hydroxylase-positive neurons. These precursor cells provide an accessible source for autologous transplantation in CNS, PNS, spinal cord and other damaged tissues.

The present invention relates to a method of producing neurons that express the enzyme tyrosine hydroxylase (TH) by subjecting neural stem cells to FGF-1, a protein kinase A activator, a protein kinase C activator, and dopamine/L-DOPA. Surprisingly, when forskolin is used as a protein kinase A activator, it requires only low levels of FGF-1 and forskolin to efficiently produce TH positive neurons from fetal or adult neural stem cells. Also provided are compositions used to produce TH positive neurons and the resulting neural cell culture, as well as a method of treating disease or conditions which are associated with dopamine neuron loss or dysfunction.

The identification of mutations in NURR1 provides molecular tools for the development of diagnostic, prophylactic and therapeutic agents for Parkinson's Disease. In specific embodiments, two point mutations are identified in exon 1 of the NURR1 gene in 10/107 (9.3%) cases of familial Parkinson's disease (PD). The mutations reduce NURR1 gene expression (mRNA and protein levels) by 87–95% and decrease tyrosine hydroxylase (a rate-limited dopamine synthesis enzyme) gene expression in vitro. It is also demonstrated that in vivo NURR1 mRNA levels in the lymphocytes from the PD patients with the exon 1 mutation are reduced by 68–84%, and in over 50% sporadic PD patients the NURR1 mRNA levels in lymphocytes are significantly reduced. A homozygous polymorphism is identified in intron 6 of NURR1 that correlates with the presence of Parkinson's disease. A splicing variant in NURR1 exon 5 is identified.

The present disclosure provides a variant tyrosine hydroxylase that provides for increased production of L-DOPA in a host cell that expresses the tyrosine hydroxylase. The present disclosure provides nucleic acids encoding the variant tyrosine hydroxylase, and host cells genetically modified with the nucleic acids. The present disclosure provides methods of making L-DOPA in a host cell. The present disclosure provides methods of making a benzylisoquinoline alkaloid (BIA), or a BIA precursor. The present disclosure provides methods of detecting L-DOPA level in a cell. The present disclosure provides methods of identifying tyrosine hydroxylase variants that provide for increased L-DOPA production; and methods of identifying gene products that provide for increased tyrosine production.

The invention relates to a pharmaceutical composition for preventing and treating Parkinson's disease. The pharmaceutical composition consists of active ingredients and medically acceptable auxiliary materials, and is characterized in that the active ingredients consist of the following components in percentage by weight: rhizoma acori graminei volatile oil extracted from rhizoma acori graminei accounting for 25-45 percent and tortoise plastron water extract extracted from tortoise plastron accounting for55-75 percent. By adopting the pharmaceutical composition, neurological integrals of Parkinson's model rats can be obviously improved, the content of monoamine neurotransmitters in rat brains is increased, reduction of tyrosine hydroxylase in brain is inhibited, and the effect of preventing and treating the Parkinson's disease is obvious.

The invention provides a metal-organic framework-superoxide dismutase assembly, a preparation method and an application thereof in preparation of drugs for treating Parkinson, and belongs to the technical field of biology. The framework makes use of biomimetic mineralization assembly strategy to immobilize SOD enzyme molecules into a metal-organic framework ZIF-8, coordination bonds are formed between SOD amino and zinc ions of ZIF-8, so that metal organic framework-SOD enzyme assembly (SOD@ZIF-8) are constructed based on enzymes. The temperature stability of SOD enzyme molecules and pH tolerance are improved through the frame work, by treating the SOD@ZIF-8 assembly as a therapeutic drug, at the cellular level, active oxygen produced by stimulation of MPP+ can be removed effectively, so as to relieve apoptosis caused by active oxygen; at the animal level, after intravenous chemotherapy by the assembly, the barrier in sports ability of Parkinson model mouse constructed by MPTP can be relieved, the expression level of tyrosine hydroxylase in substantia nigra is improved, the therapeutic effect is good.

The present invention relates to a novel gene expression system comprising: a) a first nucleotide sequence encoding a fusion polypeptide of: a1) a destabilizing domain (DD) based on DHFR, and a2) a GTPcyclohydrolase 1 (GCH1) polypeptide, or a biologically active fragment or variant thereof; and b) a second nucleotide sequence encoding a tyrosine hydroxylase (TH) polypeptide, or a biologically active fragment or variant thereof. The invention also relates to use of this gene expression system together with a ligand binding to a destabilizing domain (DD) based on dihydrofolate reductase (DHFR) for treatment of diseases associated with a reduced dopamine level, such as Parkinson's disease.

This invention relates to methods of regulating the effect of tyrosine hydroxylase (TH). In particular it relates to increasing the effective amount of TH in the central nervous systems (CNS) for the purpose of increasing TH-mediated dopamine production in the treatment of conditions such as Parkinson's disease.

The present disclosure provides methods of treating or preventing a substance-related disorder using Hsp90 inhibitors, Hsp90 modulators, tyrosine hydroxylase modulators, and modulators that reduce the interaction between Hsp90 and tyrosine hydroxylase.

Mutations in the leucine-rich repeat kinase (LRRK2) gene cause late-onset autosomal dominant Parkinson's disease (PD) with pleiomorphic pathology. Previously, we and others found that expression of mutant LRRK2 causes neuronal degeneration in cell culture. Here we used the GAL4/UAS system to generate transgenic Drosophila expressing either wild-type (WT1) human LRRK2 or LRRK2-G2019S, the most common mutation associated with PD. Expression of either WT1 human LRRK2 or LRRK2-G2019S in the photoreceptor cells caused retinal degeneration. Expression of WT1 LRRK2 or LRRK2-G2019S in neurons produced adult-onset selective loss of dopaminergic neurons, locomotor dysfunction, and early mortality. Expression of mutant G2019S-LRRK2 caused a more severe parkinsonism-like phenotype than expression of equivalent levels of WT1 LRRK2. Treatment with L-DOPA improved mutant LRRK2-induced locomotor impairment but did not prevent the loss of tyrosine hydroxylase (TH)-positive neurons. To our knowledge, this is the first in vivo “gain-of-function” model which recapitulates several key features of LRRK2-linked human parkinsonism. These flies may provide a useful model for studying LRRK2-linked pathogenesis and for future therapeutic screens for PD intervention.

Provided is a method for the derivation of neural stem cells (NSCs) from embryonic stem cells (ESCs) and the use of the NSCs for treatment of various neural disorders. The NSCs that are derived from the ESCs are tissue-specific multipotent NSCs with a stable growth rate, unlimited self-renewal capacity, and a predictable differentiation profile. Being both non-tumorigenic and engraftable, the NSCs of the present invention have utility in repopulation stroke-damaged tissue. The NSCs of the present invention may be differentiated to produce tyrosine-hydroxylase expressing neurons, which may be used as a source of dopaminergic neurons for subjects suffering from a condition characterized by dopaminergic dysfunction, such as Parkinson's disease.

The invention relates to the field of bioengineering, and particularly discloses recombinant plasmids for producing hydroxyl salidroside and genetically engineered bacteria and application of the recombinant plasmids and the genetically engineered bacteria. According to the invention, tyrosine hydroxylase BvTH, AAS enzyme gene and glycosidase UGTs gene are respectively cloned to a plasmid vector pTrc99a to obtain recombinant plasmids PTAX4511 and RrTG1068, and then the recombinant plasmids are transferred into engineering bacteria NVSL4869; through overexpression of tyrosine hydroxylase BvTH,AAS enzyme gene and glycosidase UGTs gene, saccharomyces cerevisiae can obtain the capacity of producing target enzyme, so that the purpose of producing hydroxyl salidroside is achieved. The strain and plasmid disclosed by the invention can be used for producing a downstream derivative hydroxyl salidroside of an important drug molecule salidroside by taking tyrosine as a substrate under the condition of not influencing the survival of saccharomyces cerevisiae, so that the application of salidroside in pharmacology and medicine is broadened.

The invention relates to the biomedical field, in particular to a parkinsonism mouse model, a method for establishing the parkinsonism mouse model and application of the parkinsonism mouse model. The invention transfers an extrinsic BAG5-Flag expression cassette to a genome of the animal model, and the expression cassette comprises: (a) a promoter of the rat tyrosine hydroxylase, (b) a part of Beta-globin gene and BAG5-Flag, and (c) a human somatotropin mini gene. The invention also provides the method for establishing the parkinsonism mouse model, and the parkinsonism mouse model obtained by the method of the invention can be used for studying an ubiquitin-protein degradation system and a pathology process mechanism, and screen medicine applied to delay and treatment of parkinsonism.

The serial medicine carriers are named polypeptide mediated penetrating vector and belongs to membrane penetrating peptide family. They have the functions of penetrating cell membrane and cytoblast membrane, and may carry medicine molecule to penetrate physiological barriers, such as cell membrane, blood brain barrier, placenta barrier, etc. The new carrier-tyrosinie hydrozylase fusion protein is one new kind of protein with the features of both new carrier and tyrosinie hydrozylase, and it may reach human brain substantia nigra pathologic change part via blood brain barrier to treat parkinsonism.

The invention discloses a seabuckthorn fruit oil or full-fruit oil, which is characterized by the following: fitting for treating multiple senile deforming nerve disease, such as dementia Alzheimer's disease, paralysis agitans, vessel ischemic dementia, studying memory degeneracy, senile amnesia or asomnia and so on; increasing gladioline estrogen-beta receptor obviously; making tyrosine hydroxylase, granulocyte colony stimulating factor, vessel esoderma growth factor and cell factor breed effectively; simplifying the drug component; improving effectiveness and security; cutting down the drug.

The present invention relates to a trigenic cell expression system, and includes constituting adeno-associated virus (AAV) vector rAAV/TH, rAAV/AADC and rAAV/GCH-I carrying tyrosine hydrozylase (TH), aromatic amino acid decarboxylase (AADC) and guanylyl cyclohydrolase-I (GCH-I); co-transfecting these three kinds of plasmid to packing cell by means of calcium phosphate mediation process to obtain AAV-TH, AAV-AADC and AAV-GCH-I virus grains with high titer and infection activity; collecting virus supernatant and infecting the expression cell. The present invention also relates to double gene cell expression system of TH and AADC.