90 results about "Dopaminergic neuron" patented technology

The invention discloses a Parkinson's disease animal model, a construction method and application, and relates to the field of animal genetic engineering and disease model construction. According to the model, seven mutation sites related to the human familial Parkinson's disease are introduced behind an initiation codon of a fourth exon of an endogenous SNCA gene, and the mutation sites are A18T, A29S, A30P, E46K, H50Q, G51D and A53T and have genotypes related to the human familial Parkinson's disease. The pig model shows nigra dopaminergic neuron reduction and cortical neuron reduction in the newborn period, and the core pathological process of the human Parkinson's disease can be systematically reproduced. The model can be widely applied to Parkinson's disease pathogenesis research, drug screening and cell therapy effect evaluation, and has important scientific research and preclinical application values.

The invention provides a pharmaceutical composition containing polypeptide and application of the pharmaceutical composition to preparation of a medicine for preventing and treating Parkinson's disease, and belongs to the technical field of polypeptide and biology. The amino acid sequence of the polypeptide is PCVLYDLREKM, the damage of 6-OHDA induced BZ555 nematode dopaminergic neurons can be obviously relieved, mouse dyskinesia caused by a Parkinson's disease model can be obviously improved, the spontaneous standing frequency can be improved, the movement speed in an open field can be increased, and meanwhile the IL-1beta and IL-18 levels caused by the mouse Parkinson's disease model can be reduced; the polypeptide provided by the invention can significantly reduce MAO-B level while significantly increasing DA level in nigra of brain tissues of rats with Parkinson's disease, which prompts that the polypeptide provided by the invention has a significant therapeutic effect on Parkinson's disease, and has a wide market prospect in many fields such as health food and medicine.

This invention relates to the technical field of stem cell induction differentiation and transplantation therapy, specifically to a method for inducing human induced pluripotent stem cells to differentiate into dopaminergic neuronal progenitor cells, comprising the following steps: S1, human induced pluripotent stem cells are induced to differentiate into primitive neuroepithelial cells under the action of SB431542, DMH1, SHH, FGF8b, Purmorphamine, and CHIR99021; S3, intermediate primitive neuroepithelial cells are continuously induced to differentiate using BDNF, GDNF, AA, N2, B27 (without added vitamin A), cAMP, and GlutaMax to obtain dopaminergic neuronal progenitor cells. The dopaminergic neuronal progenitor cells obtained using the method provided by this invention can survive for a long time in the brain microenvironment of Parkinson's rats and have a significant repair effect on rat motor dysfunction.

The invention relates to application of 1-allyl piperazine or pharmaceutically acceptable salt thereof in preparation of a medicine for treating Parkinson's disease. A caenorhabditis elegans PD model is adopted to prove for the first time that on one hand, 1-allyl piperazine can obviously enhance autophagy activity in a model animal body, efficiently promote removal of aggregation alpha-synuclein and radically relieve damage of Parkinson's disease characteristic pathological protein deposition to neurons, and on the other hand, 1-allyl piperazine can effectively promote removal of aggregation alpha-synuclein and radically relieve damage of Parkinson's disease characteristic pathological protein deposition to neurons. The compound can effectively activate mitochondrial unfolded protein reaction. The autophagy activation pathway and the mitochondrial function regulation pathway can generate a synergistic effect to jointly relieve the neurodegeneration process related to the Parkinson's disease, so that dopaminergic neurons are protected, and the pathological progress of the disease is delayed.

The present invention relates to the use of antimiR-27b compounds for treatment or alleviation of Parkinsons Disease. The compounds of the invention have been found to be capable of preventing dopaminergic neuronal degradation in PD models, as well as influencing important pathways relevant for development of Parkinsons Disease.

A targeting vehicles comprises an extracellular vesicle with a dopamine transporter antibody on a transmembrane protein of the extracellular vesicle, the extracellular vesicle is secreted by a cell transfected with a vector gene, and at least a portion of the vector gene comprises SEQ ID No: 1. The targeting vehicles provided in the present invention can be loaded with drugs and cross the blood-brain barrier to achieve specific binding to dopamine neuron, and regulate the secretion of Parkinson's disease marker proteins and delay the course of Parkinson's disease.

The present disclosure provides methods of differentiating pluripotent stem cells, including inducible pluripotent stem cells, into lineage-specific midbrain floor progenitor cells, decisive dopaminergic neuron progenitor cells, definitive dopaminergic neuron progenitor cells, and / or dopaminergic neuron cells. Also provided are compositions use thereof, such as for the treatment of neurodegenerative diseases and conditions, including Parkinson's disease, as well as articles of manufacture and kits for use thereof.

Described herein, inter alia, are modulators of the Nurr1 receptor and uses thereof. In one aspect, provided is a method for treating a disease associated with dysregulation and / or degeneration of dopaminergic neurons of the central nervous system in a subject in need thereof, the method comprising administering to the subject in need thereof a therapeutically effective amount of a compound described herein.

The application provides a midbrain organoid and a preparation method and application thereof. The midbrain organoid is obtained in vitro by using pluripotent stem cells, can simulate the development and maturation rules of nerve cells in vivo, provides a solid foundation for later researches such as building a drug screening platform and modeling of diseases related to dopaminergic neurons, and opens up a new way for cell replacement therapy.

Novel methods are disclosed for treating patients with Parkinson's disease and other primary and secondary parkinsonian disorders by improving cell engraftment. Treating patients with antihyperlipidemic drugs and / or CSF-1R antagonists before, during, and / or after transplantation of DA neurons improves cell viability, engraftment, proliferation, migration, or differentiation of the administered DA neurons. Methods are disclosed for pre-treating patients to improve engraftment of administered cells. Methods are disclosed for pre-treating patients to improve engraftment of administered progenitor cells.

The application discloses application of leucyl phenylalanine in preparation of a medicine for Parkinson's disease. Specifically, it is found that leucyl phenylalanine can relieve dopamine neuron dendrite degeneration of a Caenorhabditis elegans model of Parkinson's disease, enhance autophagy level, and improve proteasome activity, thereby providing an effective treatment scheme for treating Parkinson's disease.

This provides a molecular diagnostic tool useful for the efficient and accurate characterization of the discriminative and functional properties of iPSC-derived dopaminergic neurons. [Solution] A computer-based method for identifying determined dopaminergic progenitor cells within an in vitro population of neural progenitor cells is provided, comprising: receiving a test dataset containing data such as gene expression profile information relating to an in vitro population of neural progenitor cells; querying a gene expression reference database and comparing the test dataset with the gene expression reference database, wherein the gene expression reference database contains gene expression profile information of the desired determined dopaminergic progenitor cells; and outputting a computer-calculated label classification that includes an indication of whether or not the in vitro population of neural progenitor cells contains the determined dopaminergic progenitor cells.

The present invention provides a method for producing dopaminergic neuron progenitor cells from pluripotent stem cells, which method comprises the steps of: (i) performing adherent culture of pluripotent stem cells on an extracellular matrix in a medium containing a reagent(s) selected from the group consisting of BMP inhibitor, TGFβ inhibitor, SHH signal-stimulating agent, FGF8, and GSK3β inhibitor; (ii) collecting Corin- and / or Lrtm1-positive cells from the cells obtained in Step (i) using a substance which binds to Corin and / or a substance which binds to Lrtm1; and (iii) performing suspension culture of the cells obtained in Step (ii) in a medium containing a neurotrophic factor.

The application belongs to the technical field of biological medicine, and discloses application of a simulation polypeptide containing a fibrinogen RGD module in preparation of a medicine for preventing and / or treating Parkinson's disease. The sequence of the simulation polypeptide containing the fibrinogen RGD module is Gly-Arg-Gly-Asp-Ser-Pro-Lys-Asn-Pro-Ser-Cys. The applicant of the application finds that FG abnormally accumulates in the substantia nigra compacta of a PD mouse, and the FG excessively accumulated in the brain may promote abnormal aggregation of alpha-syn of dopaminergic neurons through mediation of an alpha v beta 3 integrin receptor. The simulation polypeptide provided by the application can effectively inhibit abnormal aggregation of alpha-syn of dopaminergic neurons caused by the abnormally accumulated FG in the brain and death of the dopaminergic neurons, improve the motor ability of the PD mouse modeled by MPTP, and provide a new target and thought for PD treatment.

The present disclosure provides methods of differentiating pluripotent stem cells, including induced pluripotent stem cells, into lineage-specific floor plate midbrain progenitor cells, determined dopaminergic neuronal progenitor cells, committed dopaminergic neuronal progenitor cells and / or dopaminergic neuronal cells. Also provided are compositions uses thereof, such as for treating neurodegenerative diseases and conditions, including Parkinson's disease, and articles of manufacture and kits for use thereof.

The invention discloses a pharmaceutical composition for preventing and / or treating Parkinson's disease and application of the pharmaceutical composition, and relates to the technical field of biological medicine. The composition comprises nervonic acid, salvianolic acid A and pharmaceutically acceptable auxiliary materials. Experiments prove that the composition can improve intestinal flora, obviously promote alleviation of symptoms of a Parkinson's disease model animal, promote regeneration of dopaminergic neuronal cells and neural stem cells, relieve neuroinflammation, promote repair of damaged nerves, improve dyskinesia of mice caused by Parkinson's disease and improve the Parkinson's disease resistance of the mice. Therefore, the polypeptide has potential application value in treatment of the human Parkinson's disease. According to the invention, the effect of the composition is confirmed from the perspective of improving the change of intestinal flora by utilizing the relationship of the brain-intestinal axis, and a basis is provided for intervening the treatment of Parkinson's disease through the intestinal flora.

Provided is a method for differentiating pluripotent stem cells in vitro to prepare a cell population mainly composed of midbrain floor plate dopaminergic progenitor cells, wherein the progenitor cells can efficiently and directionally differentiate into midbrain dopaminergic neuron precursors and midbrain dopaminergic neurons after being transplanted into a subject. Further provided is a cell population prepared by the method, a pharmaceutical composition containing the cell population, and a method for using the cell population or the pharmaceutical composition to treat or ameliorate a neurological disorder caused by a reduction in the number of midbrain dopaminergic neurons and / or impairment of function thereof.

An application of Bone Marrow Mesenchyml Stem Cell Exosomes (BMSC-Exos) in treating Parkinson's disease (PD) is provided, wherein the BMSC-Exos are generated by stimulating BMSCs with a culture solution and extracted from the culture solution after passage; and the culture solution of the BMSCs is an α-MEM culture solution containing FBS and PS. The BMSC-Exos can greatly improve a motor function of a model mouse with PD, protect dopaminergic neurons of the model mouse with PD, improve an olfactory function of the model mouse with PD, and also inhibit the activation of olfactory astrocytes of the model mouse with PD.

The application discloses an induction method for directional differentiation of neural stem cells into dopaminergic neurons, comprising the following steps: S1, activation and adhesion of NSCs; S2, directional induction of midbrain precursor cells; S3, directional induction of dopaminergic neurons; and S4, synaptic function maturation induction. The induction method for directional differentiation of neural stem cells into dopaminergic neurons can significantly improve the directional efficiency and lineage specificity of the midbrain precursor cells: by adding salvianolic acid B and icariin, and in cooperation with SHH, FGF8 and other induction factors, the midbrain lineage-specific signal pathway can be efficiently activated, the positive rate of the midbrain precursor cell marker LMX1A is increased to more than 76%, which is far better than 49% of the existing system, and abnormal differentiation of non-midbrain lineages is effectively inhibited.

The present invention provides novel irisin peptides (e.g, irisin glycosylation mutants and biologically active fragments thereof). Also provided are methods for preventing or reducing degeneration of dopaminergic neurons and / or preventing or ameliorating at least one motor deficit in a subject in need thereof, such as in a subject with α-synucleinopathy, using the novel irisin peptides to modulate irisin-induced integrin signaling. The novel irisin peptides can also be used in methods for increasing expression of brain-derived neurotrophic factor (BDNF), and / or treating or preventing neurological diseases or disorders that would benefit from decreased neuronal cell death and / or increased neuronal survival in a subject. In addition, the novel irisin peptides may be used in methods for preventing or treating muscular atrophy or muscular dystrophy.

The present disclosure provides automated methods of differentiating pluripotent stem cells, including induced pluripotent stem cells, into lineage-specific floor plate midbrain progenitor cells, such as dopaminergic neuronal progenitor cells, determined dopaminergic neuronal progenitor cells, committed dopaminergic neuronal progenitor cells and / or dopaminergic neuronal cells. Also provided are compositions uses thereof, such as for treating neurodegenerative diseases and conditions, including Parkinson's disease, and articles of manufacture and kits for use thereof.

The invention relates to the technical field of biomedical treatment, in particular to a construction method of a Parkinson's disease animal model. According to the method, a virus solution carrying taCasp3 is used for ablating dopaminergic neurons of the compact part of nigra of the brain of an animal, anxiety and depression behaviors of the animal are induced, and the animal model of the Parkinson's disease is obtained. The Parkinson's disease animal model can stably reproduce nervous and psychiatric symptoms such as anxiety and depression, and is of great significance to improvement and treatment of anxiety or depression symptoms of Parkinson's disease.

The invention discloses an application of Lumacaftor in the treatment of Parkinson's disease. The treatment effect of Lumacaftor on PD is verified through in-vitro cell experiments and in-vivo animal experiments respectively, and it is found that after Lumacaftor is used in a microglial cell-neuron co-culture PD cell model, apoptosis pathway related protein in neurons is remarkably reduced compared with a model group; after Lumacaftor treatment is performed on a PD mouse in an MPTP mouse PD model, dopaminergic neurons of the PD mouse are remarkably increased, and the motor function is improved. The application provides a new thought for effective treatment of PD, and the application prospect is wide.

The invention provides a construction method and application of a human dopaminergic neuron Zika virus infection model, and belongs to the technical field of disease model preparation. According to the invention, dopaminergic neurons induced by hiPSCs are taken as research objects, and a Zika virus infected human-derived dopaminergic neuron model is established. The human-derived dopaminergic neuron model can be used for effectively screening drugs with antiviral activity. The virus infection model constructed by the invention lays a foundation for effectiveness and safety screening of subsequent drugs.

A cell population comprising Corin- and / or Lrtm1-positive cells was produced by the following steps (1) and (2), from which Corin positive and / or Lrtm1 positive cells are collected using a substance that binds to Corin and / or a substance that binds to Lrtm1, and dopaminergic neuron progenitor cells are produced by performing suspension culture of the Corin positive and / or Lrtm1 positive cells in a culture solution containing one or more nutritional factors:(1) a step of performing adhesion culture of pluripotent stem cells in a medium for maintaining undifferentiated state containing a Sonic hedgehog (SHH) signal stimulant, and an undifferentiated state-maintaining factor in the absence of feeder cells but in the presence of an extracellular matrix, and(2) a step of culturing the cell population obtained in the step (1) in a culture solution containing one or more differentiation-inducing factors.

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.

Provided are methods for in vitro induced differentiation of embryonic stem cells or pluripotent stem cells into dopaminergic neural progenitor cells, dopaminergic neural precursor cells and / or dopaminergic neurons. Also provided are media for use in the method, cell populations obtained using the method, and the use of the obtained cell populations in the prevention and / or treatment of diseases and / or dysfunctions associated with dopaminergic neuron degenerative disorders.

The invention provides an induction method for directionally differentiating neural stem cells into dopaminergic neurons. The induction method comprises the following steps: (1) electroporating the neural stem cells, and enabling a 40-80nm Fe2O3 (at) TGA (at) MIL-100 (at) PDA (at) Ag nano material to enter the neural stem cells; and (2) placing the neural stem cells in the step (1) in a 0.25-0.4 Tesla magnetic field, rotating the neural stem cells in the horizontal direction for 10-20 minutes without changing the magnetic field intensity, then culturing the neural stem cells, controlling the induced electromotive force induced by the rotating magnetic field to be 0.1-10 mV, rotating the magnetic field direction for 10-20 minutes every 23-25 hours, and culturing the neural stem cells for 72-240 hours. According to the induction method, the dopaminergic neuron differentiation rate is high, the synaptic function maturity is improved, the dopaminergic neuron differentiation rate exceeds 80%, the synaptic function maturity is improved compared with a traditional method, the induction method can be applied to Parkinson's disease treatment and nervous system injury repair, and an efficient induction technology is provided for cell treatment of nervous system degenerative diseases and injuries.

The invention discloses a class of euphorbia kanane type triterpenoids as well as a preparation method and application thereof. The euphorbia kanane type triterpenoids are extracted and separated from Chinese quassia tree, four of the euphorbia kanane type triterpenoids are new compounds, and the rest of the euphorbia kanane type triterpenoids are known compounds. The applicant finds that most of the compounds show remarkable anti-neuroinflammation activity through activity screening. In an MPTP-induced PD mouse in-vivo model, part of the compounds can significantly improve the impaired movement behavior of PD mice; in addition, MPTP-induced brain tissue inflammatory response can be effectively inhibited, and a protection effect on dopaminergic neurons is achieved.