60 results about "Tyrosine hydroxylase" patented technology

The present invention relates to a novel pomalidomide derivative that exhibits improved pharmacological effects compared to pomalidomide, and is used to treat brain diseases. The novel pomalidomide derivative developed in the present invention has excellent binding ability to cereblon, is almost non-cytotoxic, has low possibility of teratogenic side effects, and can regulate TNF-α expression, as well as suppress oxidative stress and has excellent in vivo pharmacokinetic stability, and shows excellent effects of improving the decrease in motor ability, which is a symptom of Parkinson's disease, and increasing the expression of tyrosine hydroxylase, which is decreased in Parkinson's disease, and can be used for the prevention or treatment of brain diseases such as Parkinson's disease.

The invention provides application of scEMC10 in treatment and diagnosis of cerebral vascular endothelial cell senescence, and relates to the technical field of biomedicine. The research of the inventor finds that brain microvascular endothelial cell senescence is caused by the lack of scEMC10; after the brain microvascular endothelial cells are treated by scEMC10, beta-galactosidase, SASP and classic senescence markers related to senescence can be down-regulated; after scEmc10 is supplemented to old mice and Alzheimer's disease 5XFAD model mice, the motion coordination ability and the spatial cognitive ability of the mice can be obviously improved, the relative content of a marker phosphorylated alpha-synuclein of the Parkinson's disease of the old mice can be obviously reduced, and the content of tyrosine hydroxylase phosphorylated active forms can be increased. Therefore, the scEMC10 can be used for treating brain microvascular endothelial cell senescence, improving Alzheimer's disease and Parkinson's disease and detecting brain microvascular endothelial cell senescence as a marker.

The invention belongs to the technical field of biological medicines, and relates to application of achyranthes bidentata polypeptide combined with human umbilical cord mesenchymal stem cell exosome in preparation of a medicine for preventing and / or treating Parkinson's disease, the achyranthes bidentata polypeptide combined with the human umbilical cord mesenchymal stem cell exosome is used for treating mice, and 1-methyl-4-phenyl-1, 2, 3, 4-tetramethyl-1, 3, 4-tetramethyl-1, 3, 4-tetramethyl-1, 3, 4-tetramethyl-1, 3, 4-tetramethyl-1, 3, 4-tetramethyl-1, 3, 4 The method comprises the following steps: carrying out Parkinson model (PD) modeling on a mouse by using 2, 3, 4, 6-tetrahydropyridine (MPTP); it is found that the treatment can significantly relieve PD related symptoms, for example, the number of dopaminergic neurons in a nigra part is recovered, expression of tyrosine hydroxylase in a middle brain part is improved, movement and olfactory dysfunction of a PD model mouse is relieved, activation of olfactory bulbs and microglia and astrocytes in the middle brain part is reduced, and activity of neurons in the olfactory bulbs is improved.

The invention relates to an engineering strain for producing (S)-higenamine, a method and application. The engineering strain is a recombinant pichia stipitis engineering strain containing coding genes of exogenous tyrosine hydroxylase mutants TyrHW13L and F309L, a dopa decarboxylase DODC and a higenamine synthase NCS. The recombinant pichia stipitis engineering strain is a recombinant pichia stipitis engineering strain containing coding genes of the exogenous tyrosine hydroxylase mutants TyrHW13L and F309L. According to the engineering strain, (S)-higenamine can be synthesized through a whole-cell catalytic reaction one-step method, exogenous coenzyme and exogenous reducing power are not needed, and the endogenous reducing power of the strain is utilized; the reaction path is short, products can be quickly accumulated in a short time, and the catalytic efficiency is high; the production cost is reduced.

The present invention relates to a recombinant microbial host cell comprising an operative biosynthetic metabolic pathway capable of producing one or more compounds selected from the group consisting of L-dopa, dopamine, (S)-Norcoclaurine and derivatives thereof; said pathway comprising a heterologous L-tyrosine hydroxylase (TyrH) converting L-Tyrosine into L-dopa capable of increasing the cell production of the Compound compared to a reference L-tyrosine hydroxylase having the sequence set forth in SEQ ID NO: 58.

Aspects of the disclosure relate to tyrosine hydroxylases, including engineered enzymes, and their use in catalyzing chemical reactions to produce betalain. Additional aspects of the disclosure relate to genetic modifications of host cells to improve betalain production.

The invention belongs to the technical field of disease and pest control, discloses application of tyrosine hydroxylase as a target spot in prodenia litura pest control for the first time, screens out a dopamine synthesis inhibitor AMPT aiming at tyrosine hydroxylase, and develops a technology for efficiently controlling prodenia litura. According to the technology, AMPT is injected into the fourth-instar larvae of the prodenia litura, and the melanin deposition of the exoskeleton of the larvae is reduced, the color of the body surface becomes light and the athletic ability is remarkably reduced by utilizing the dopamine synthesis inhibition function of AMPT. On one hand, reduction of melanin deposition weakens the environmental adaptability of pests, and the exposure risk of the pests in the natural environment is increased; on the other hand, the migration behavior of the pests is directly influenced by the decline of the exercise ability, and the population diffusion and hazard range of the pests are limited. The dual-action mechanism reduces the environmental adaptability and survival competitiveness of the pests, and provides a new strategy for green prevention and control.

The present invention belongs to the field of biotechnology, and particularly relates to a bionic synthesis engineering bacterium of compound Danshen and its application. The engineering bacterium is obtained by introducing cytochrome P450 reductase, tyrosine hydroxylase and D-lactate dehydrogenase of Lactobacillus pentosus on the basis of a Saccharomyces cerevisiae starting bacterium that produces protopanaxadiol, cryptotanshinone diene and borneol. The obtained Saccharomyces cerevisiae genetic engineering bacterium can simultaneously synthesize the active ingredients of compound Danshen preparations, namely protopanaxadiol, cryptotanshinone diene, danshensu and borneol, and has application value.

The present invention relates to a use of a novel pomalidomide derivative which is for treating brain diseases, and exhibits improved pharmacological effects as compared to pomalidomide. The novel pomalidomide derivative according to the present invention exhibits excellent binding to cereblon, has almost no cytotoxicity, is unlikely to cause teratogenic adverse effects, can control TNF-α expression, exhibits excellent in vivo pharmacokinetic stability while suppressing oxidative stress, ameliorates a decrease in motor function which is a symptom of Parkinson's disease, and increases tyrosine hydroxylase expression which is reduced by Parkinson's disease, and thus can be used for preventing or treating brain diseases such as Parkinson's disease.

The invention belongs to the technical field of biology, and particularly relates to application of a transcription factor NR2F1 in regulation and control of tyrosine hydroxylase synthesis. The transcription factor NR2F1 is combined with a tyrosine hydroxylase coding gene promoter region to interact with a TH gene to regulate the expression of the TH gene, and the transcription factor NR2F1 has an important regulation effect on synthesis of tyrosine hydroxylase and provides a new target and a new idea for clinical treatment of tyrosine hydroxylase imbalance related diseases.

The invention belongs to the technical field of medicines, and discloses application of poliumoside to prevention and treatment of Parkinson's disease. Specifically, the invention discloses application of poliumoside as a compound shown in a formula (I) in the aspect of preventing and treating Parkinson's disease. Pharmacological experiments prove that after 14 days of administration of the poliumoside, the impairment of motor coordination function caused by MPTP-induced Parkinson's disease can be obviously improved, the reduction of the expression level of brain nigra tyrosine hydroxylase caused by MPTP is improved, and the result shows that the poliumoside has obvious pharmacological activity for preventing and treating Parkinson's disease. Therefore, poliumoside can be used for preparing the medicine for preventing and treating Parkinson's disease, and has high clinical application value and development prospect.

The invention belongs to the technical field of novel application of nattokinase, and provides application of nattokinase in preparation of a medicine for preventing and / or treating Parkinson's disease. According to the invention, an MPTP / MPP + induced Parkinson's disease (PD) in-vivo and in-vitro model is established, and a neuroprotection mechanism of nattokinase is disclosed by adopting a systematic experiment method. Results show that the nattokinase can significantly improve dyskinesia and intestinal dysfunction of MPTP-induced PD mice; the damage of dopaminergic neurons of the middle brain is effectively relieved, and the density of tyrosine hydroxylase positive neurons is maintained; the expression of TLR4 and NLRP3 inflammasome pathways and related proinflammatory cytokines is inhibited, and the neuroinflammatory response is relieved; pINK1 / Parkin expression is up-regulated, mitochondrial autophagy is activated, and damaged neurons are cleared. Direct association between nattokinase and Parkinson's disease prevention and treatment is established for the first time, an innovative solution is provided for developing a novel anti-Parkinson's disease medicine with dual effects of motor function improvement and neuroprotection, and the application has important development value in the field of treatment of neurodegenerative diseases.

The application provides an application of scEMC10 in treatment and diagnosis of brain vascular endothelial cell aging, and relates to the technical field of biomedicine. The inventor finds that scEMC10 deficiency leads to brain microvascular endothelial cell aging; brain microvascular endothelial cells treated by scEMC10 can down-regulate beta-galactosidase, SASP and classic aging markers related to aging; after old mice and 5XFAD model mice of Alzheimer's disease are supplemented with scEmc10, the movement coordination ability and spatial cognitive ability of the mice can be obviously improved, and the relative content of the Parkinson's disease marker, phosphorylated alpha-synuclein, of the old mice can be obviously reduced, and the content of the tyrosine hydroxylase phosphorylation activity form can be increased. Therefore, scEMC10 can be used for treatment of brain microvascular endothelial cell aging, improvement of Alzheimer's disease and Parkinson's disease, and detection of brain microvascular endothelial cell aging as a marker.

A genetic construct comprises a promoter operably linked to a first coding sequence, which encodes tyrosine hydroxylase (TH), and a second coding sequence, which encodes GTP cyclohydrolase 1 (GCH1), wherein the second coding sequence is 3′ to the first coding sequence, and the first and second coding sequences are part of a single operon. The genetic construct does not encode aromatic amino acid decarboxylase (AADC).

The invention relates to a lentiviral vector comprising a tricistronic expression cassette encoding: - tyrosine hydroxylase of SEQ ID NO 1; - GTP cyclohydrolase I of SEQ ID NO 2; and - aromatic L-amino acid decarboxylase of SEQ ID NO 3, or a functional variant of said enzymes having a nucleic sequence that is at least 80% identical to SEQ ID NOs 1, 2 and 3. The vector is characterised in that the three enzymes are expressed under the control of the same human PGK-1 promoter, or a functional variant of said human PGK-1 promoter having a nucleic sequence that is at least 80% identical to SEQ ID NO 4.

The present invention belongs to the field of biotechnology. Specifically, it relates to the use of the transcription factor NR2F1 in regulating the synthesis of tyrosine hydroxylase. The present invention provides that the transcription factor NR2F1 interacts with the TH gene by binding to the promoter region of the tyrosine hydroxylase-encoding gene, regulates its expression, and has an important regulatory effect on the synthesis of tyrosine hydroxylase, providing new targets and new ideas for the clinical treatment of diseases related to tyrosine hydroxylase imbalance.

The invention discloses application of C-176 in preparation of a medicine for treating Parkinson's disease, belongs to the technical field of medicines, and particularly relates to a medicine for treating Parkinson's disease, which comprises C-176 or a pharmaceutical salt thereof. As an STING inhibitor C-176 is adopted as a medicine for treating Parkinson's disease, 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) is utilized to construct an animal model of Parkinson's disease, and animal experiments prove that the expression of STING protein in striatum of a mouse in the model is increased, and the expression of tyrosine hydroxylase (TH) is reduced at the same time. The C-176 can improve the expression level of TH in striatum of a Parkinson model mouse. A behavioral experiment result proves that the C-176 can improve the movement and movement coordination ability of a model mouse and relieve the anxiety behavior of the model mouse.

A pharmaceutical or health food composition for preventing or treating Parkinson's disease containing O-cyclic phytosphingosine-1-phosphate. The composition can prevent the death of SH-SY5Y nerve cells, which are dopaminergic nerve cells, and increase the expression of tyrosine hydroxylase, an enzyme required for dopamine formation. Accordingly, the composition can be effectively used for preventing or treating Parkinson's disease.

The invention belongs to the technical field of biology, and particularly relates to compound salvia miltiorrhiza biomimetic synthesis engineering bacteria and application thereof. The engineering bacterium is obtained by introducing cytochrome P450 reductase, tyrosine hydroxylase and D-lactic dehydrogenase of lactobacillus pentosus on the basis of starting bacteria of saccharomyces cerevisiae for producing protopanoxadiol, hypotanshinone diene and borneol. The obtained saccharomyces cerevisiae genetically engineered bacterium can be used for simultaneously synthesizing active ingredients of protopanoxadiol, hypotanshinone diene, tanshinol and borneol of a compound salvia miltiorrhiza preparation, and has application value.

The invention discloses an application of a smoked plum general flavone extract in preparation of a medicine for preventing or treating Parkinson's disease, and relates to the field of medicines.The smoked plum general flavone extract is prepared through a method comprising the following steps that smoked plum serves as a raw material and is extracted through an ethanol water solution, an extracting solution is concentrated and then adsorbed through macroporous resin, and the smoked plum general flavone extract is obtained. Eluting with an ethanol water solution, collecting the eluent, concentrating and drying; the application shows a definite neuroprotective effect in two classical animal models of Parkinson's disease, can reduce loss and morphological damage of brain nigra neurons in model animals, and significantly increases the number of tyrosine hydroxylase positive cells in nigra of the model animals, which indicates that the application has a protective effect on dopaminergic neurons, and can be used for preparing drugs for treating Parkinson's disease. Motion coordination and balance capacity of model animals can be obviously improved in a dose-dependent manner, the potential of improving disease progress is achieved, and a new candidate substance is provided for developing Parkinson's disease treatment drugs with a neuroprotective effect.

The present invention relates to a recombinant microbial host cell comprising an operative biosynthetic metabolic pathway capable of producing one or more compounds selected from the group consisting of L-dopa, dopamine, (S)-Norcoclaurine and derivatives thereof; said pathway comprising a heterologous L-tyrosine hydroxylase (TyrH) converting L-Tyrosine into L-dopa capable of increasing the cell production of the Compound compared to a reference L-tyrosine hydroxylase having the sequence set forth in SEQ ID NO: 58.

The present invention relates to cannabidiol derivatives, their preparation methods and uses, particularly in the treatment of nervous system disorders (e.g. The present invention discloses the use of the above cannabidiol in the prevention and treatment of chronic kidney disease (such as Parkinson's disease). The derivatives were screened from a series of synthetic derivatives, and the results of animal experiments showed that The above cannabidiol derivatives improved the balance beam scores of Parkinson's disease model animals. It reduces dopamine levels and tyrosine hydroxylase (T hydroxylase) levels in the substantia nigra (SubN) of the brain. H) It can improve the positive rate of cells and treat various diseases such as epilepsy and Parkinson's disease. It is useful in the research and development of therapeutic drugs for diseases, and has high application value.

Disclosed in the present invention are a cannabidiol derivative, a preparation method therefor and an application thereof, particularly an application in preventing and treating nervous system diseases (such as Parkinson's disease). The cannabidiol derivative is obtained by screening from a series of synthetic derivatives. An animal testing result shows that the cannabidiol derivative can reduce the balance beam score of a Parkinson's model animal and improve the dopamine level and the tyrosine hydroxylase (TH) cell positive rate in substantia nigra (SubN), can be used for drug development and research of various diseases such as epilepsy and Parkinson's disease, and has better application value.

The invention belongs to the technical field of recombinant protein preparation, and particularly relates to a production and preparation method of recombinant mussel mucin rich in dopa. By optimizing the gene sequence of the mussel mucoprotein and combining with a pichia pastoris expression system, efficient secretory expression of recombinant protein is realized, and the problem of low natural extraction yield is solved. The immobilized tyrosine hydroxylase is used for in-vitro dopa modification, and the enzyme can be recycled through a magnet, so that the cost is reduced, and the economy and sustainability of the modification reaction are improved. Reaction parameters are optimized, so that a suitable environment is provided for enzymatic reaction, and the dopa modification efficiency is improved. Nitrogen is used for protection in the purification process, ascorbic acid and EDTA are added into a buffer solution, oxidation inactivation of dopa is avoided, and the structural integrity and the adhesion function of the target protein are ensured. And through a combined purification strategy of anion exchange chromatography and gel filtration chromatography, impurities are effectively removed, and the high-purity dopa recombinant mussel mucin is obtained.

The present invention discloses a cannabidiol derivative, its preparation method and application, especially the application in the prevention and treatment of nervous system diseases (such as epilepsy, Parkinson's disease). The above-mentioned cannabidiol derivative is screened from a series of synthetic derivatives. The results of animal experiments show that these compounds can effectively shorten the duration of epileptic seizures in experimental animals, improve the symptoms of epileptic seizures in experimental animals, reduce the balance beam score of Parkinson's model animals, increase the dopamine level and the positive rate of tyrosine hydroxylase (TH) cells in the substantia nigra (SubN) of the brain, and can be used for the drug development and research of various diseases such as epilepsy and Parkinson's disease, and has better application value.

The present disclosure provides, in part, engineered tyrosine hydroxylase (TH) promoters, vectors (e.g., viral vectors) comprising the engineered TH promoters, and uses thereof for improving neuronal-type specific epigenome editing of neurodegenerative disease relevant genes (e.g., SNCA).

The invention discloses application of tyrosine hydroxylase in drugs for treating collagen-induced arthritis, and belongs to the technical field of biological medicines, TH expression is down-regulated by adopting a TH-shRNA plasmid, TH expression is up-regulated by adopting a plasmid for expressing the full length of a mouse TH gene, and the total length of the mouse TH gene is up-regulated. The TH-shRNA plasmid and the plasmid for expressing the full length of the TH gene of the mouse are respectively transfected with a collagen induced arthritis (CIA) mouse CD4 + T cell and a CIA mouse CD4 + T cell, and the imbalance condition of Th17 / Treg in the CD4 + T cell is observed. The result shows that the TH gene silencing in the CD4 + T cell of the CIA can obviously promote the imbalance of the Th17 / Treg, the TH gene overexpression in the CD4 + T cell can obviously inhibit the imbalance of the Th17 / Treg, and the Plt can obviously inhibit the TH gene overexpression in the CD4 + T cell. And 0.05%.

The invention discloses ultrasonic response ZnS (at) Lf piezoelectric nanoparticles as well as a preparation method and application thereof, and relates to the technical field of piezoelectric materials. The ultrasonic response ZnS (at) Lf piezoelectric nano-particle comprises a ZnS nano-particle and lactoferrin loaded on the surface of the ZnS nano-particle. According to the invention, lactoferrin is used as a potent brain-targeting ligand, and passes through a blood-brain barrier to be accumulated in brain parenchyma under the cell transfer action of brain capillary endothelial cells. ZnS nano particles release charges under the ultrasonic action, an electric signal activates a voltage-gated calcium ion channel and extracellular calcium ion influx, calcium ion / calmodulin kinase induces tyrosine hydroxylase (TH) phosphorylation, the activity of tyrosine hydroxylase is enhanced, tyrosine hydroxylase is a key enzyme for generating dopamine, and the activity of the tyrosine hydroxylase is enhanced. Therefore, more tyrosine in vivo is converted into neurotransmitter dopamine under the action of the enzyme. Finally, the regeneration of dopaminergic neurons is realized, so that the Parkinson's disease is effectively improved.

This invention discloses the application of bimatoprost in the preparation of drugs for the prevention and / or treatment of Parkinson's disease, within the field of drug reuse. Bimatoprost is a prostaglandin F2α analog, currently mainly used for glaucoma and eyelash growth. This invention has found that bimatoprost can improve Parkinson's disease-related behavioral disorders, increase the expression of tyrosine hydroxylase, a protein associated with dopaminergic neurons in the substantia nigra, and reduce the abnormal accumulation of α-synuclein, thus exhibiting good ameliorative and protective effects against Parkinson's disease. This invention provides a new drug option for the treatment of Parkinson's disease.

Provided are a gene therapy vector for treating Parkinson's disease and a use thereof. Specifically, provided is an adeno-associated virus (AAV) vector for treating Parkinson's disease, which can simultaneously express functional tyrosine hydroxylase (TH), GTP-cyclohydrolase 1 (GCH1) and aromatic amino acid decarboxylase (AADC) to promote dopamine synthesis. Also provided are an AAV virus particle containing the AAV vector, a composition containing the AAV vector or the AAV virus particle, and uses of the AAV vector, the AAV virus particle and the composition in the preparation of drugs for preventing or treating Parkinson's disease.