156 results about "Dopaminergic neuron" patented technology

The invention discloses an application of a CD73 + NK cell in preparation of a medicine for preventing or treating Parkinson's disease. The applicant discovers that the CD73 + NK cell can prevent dopaminergic neuron loss and glial inflammation response of the MPP + induced VM cell in the experimental process. However, TGF-beta1 and IL-10 secreted by the CD73 + NK cells do not significantly prevent loss of dopaminergic neurons induced by MPP + in cross-pore co-culture of the CD73 + NK cells and VM neurons. Therefore, the CD73 + NK cells are proved to protect dopaminergic neurons from the influence of MPP + neurotoxicity through an intercellular contact mechanism, namely CD73-SIRPA interaction.

The invention discloses novel application of notoginsenoside Rg1, namely application of the notoginsenoside Rg1 in preparation of a cathepsin D (CTSD) inhibitor, the notoginsenoside Rg1 can inhibit CTSD enzyme activity so as to recover lysosome structure and function, relieve endoplasmic reticulum stress reaction and relieve alpha-syn aggregation and dopaminergic neuron apoptosis, has a remarkable protection effect on a Parkinson's disease model, and can be used for preparing a novel anti-inflammatory drug. The invention provides a new thought and a potential drug basis for targeted intervention of Parkinson's disease. The invention discloses a new mechanism that Rg1 plays a role in neuroprotection through a CTSD-lysosome-endoplasmic reticulum stress pathway.

The invention discloses a mesenchymal stem cell membrane bionic nano-enzyme for targeted therapy of Parkinson's disease as well as a preparation method and application of the mesenchymal stem cell membrane bionic nano-enzyme. The mesenchymal stem cell membrane bionic nano enzyme comprises an inner core and a mesenchymal stem cell membrane, wherein the inner core is composed of mesoporous polydopamine nanoparticles, and the mesenchymal stem cell membrane coats the inner core. The medicine contains the mesenchymal stem cell membrane bionic nano enzyme. The mesenchymal stem cell membrane bionic nano-enzyme disclosed by the invention shows good biocompatibility, and can be homed to a Parkinson disease region in the brain under the mediation of CXCR4 and VLA-4 specific membrane proteins. In addition, through the CD47 membrane protein expressed on the surface, the removal of the immune system can be avoided, so that the action time in the body is prolonged. The nano-enzyme is helpful for eliminating reactive oxygen free radicals, reducing oxidative stress level and reducing damage of neuroinflammation to dopaminergic neurons, so that safe and efficient treatment of Parkinson's disease is realized.

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 relates to the technical field of environmental health risk evaluation, in particular to a method for evaluating the risk of Parkinson's disease induced by environmental pollutants. The method for evaluating the risk of inducing the Parkinson's disease by the environmental pollutants comprises the following steps: carrying out a subacute exposure experiment by taking caenorhabditis elegans as a model organism; observing the transport capacity of the caenorhabditis elegans, observing and counting the abnormal movement ability of the caenorhabditis elegans, and determining the lipofuscin level of the caenorhabditis elegans, the damage degree of dopaminergic neurons, the dopamine level and the expression and aggregation conditions of alpha-synuclein protein, so as to evaluate the risk of the Parkinson's disease induced by environmental pollutants; the environmental pollutant is 6: 2 chlorinated polyfluoroalkyl ether sulfonate. According to the method, the PD toxicity evaluation model is generated by constructing a behavior characteristic and molecular characteristic scheme and combining multi-strain nematode data, and the problem that in the prior art, the risk of inducing PD by environmental pollutants is difficult to comprehensively reveal due to the fact that a single dimension is concerned is solved.

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 invention discloses an experimental material for constructing a cerebral microcirculation disturbance Parkinson's disease animal model and application of the experimental material, and belongs to the technical field of animal model construction. The invention particularly relates to an experimental material for constructing a model, application of the experimental material, a model construction method and application of the model. Research finds that cerebral microcirculation disturbance can cause increase of blood brain barrier permeability, and neuronal damage aggravation caused by penetration of a large amount of inflammatory factors in systemic circulation into the brain; meanwhile, glial cells at the nerve and blood vessel coupling position are activated, tight connection between endothelial cells is damaged, and excessive active oxygen is generated, so that apoptosis of dopaminergic neurons is further aggravated. The research on the Parkinson's disease by adopting the microcirculation disturbance animal model is more in line with the actual pathophysiological environment of the Parkinson's disease patient, and the experimental result has higher reference value.

The present invention provides a C-terminal CDNF fragment sequence or a sequence which has at least 80% homology or sequence identity to said sequence. The C-terminal CDNF fragment protects ER stressed neurons, motoneurons and dopaminergic neurons and the fragment is capable of penetrating neuronal cell membrane as well as the blood-brain-barrier. The present invention further provides said fragment and pharmaceutical compositions comprising said fragment for use in treatments of degenerative diseases and disorders including central nervous system diseases, diabetes and retinal disorders. The present invention is also providing a C-terminal MANF fragment sequence or a sequence which has at least 80% homology or sequence identity to the said sequence and pharmaceutical compositions comprising said MANF fragment for use in the treatment of degenerative diseases and disorders including central nervous system diseases, diabetes and retinal disorders.

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 invention discloses nasal injection type baicalein hydrogel as well as a preparation method and application thereof. The preparation method comprises the following steps: dissolving carboxymethyl chitosan in water, stirring to form a uniform carboxymethyl chitosan solution, then adding a 4-formylphenylboronic acid / baicalein solution, and then continuously stirring until yellow transparent hydrogel is formed, namely the nasal injection type baicalein hydrogel is obtained. The hydrogel has self-healing ability and proper viscosity, can be adhered to the epithelium of the nasal cavity and is continuously released in the microenvironment of the nasal cavity, so that the brain entering efficiency of the baicalein is remarkably improved; neurotoxic oligomers formed by abnormal aggregation of alpha-syn can be reduced; neuroinflammation can be relieved by regulating and controlling phenotypic polarization of microglial cells M2; oxidative stress can be improved by removing excessive ROS, dopaminergic neuron apoptosis is reduced, and the compound can be used for treating Parkinson's disease and has a good application prospect.

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 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 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.

The invention discloses an application of miRNA (micro Ribonucleic Acid) in preparation of a medicine for preventing and treating Parkinson's disease, and particularly provides an application of miRNA, which is miR-363-3p, miR-146b-3p, miR-24-2-5p, miR-26a-5p and miR-22-3p and plays a role in neuroprotection in SKP-SC-EVs (SKP-SC-EVs). Wherein the miR-146b-3p has the best effect of improving the activity of damaged nerve cells, and can recover TCA cycle key enzyme down-regulation caused by neurotoxic substances, and inhibition of the miR-146b-3p can lead to cell activity weakening with increased SKP-SC-EVs. The invention provides miRNA for protecting dopaminergic neurons by adjusting mitochondrial functions and energy metabolism, can be applied to preparation of drugs for preventing and treating Parkinson's disease, and is beneficial to prevention and treatment of Parkinson's disease and other neurodegenerative diseases.

A method for generating human midbrain immature neurons and mature dopaminergic neurons from neural progenitor cells is provided. The immature and mature midbrain neurons are obtained from neural progenitor cells such as committed midbrain neural stem cells (NSCs) and midbrain neural progenitor cells (midbrain NPCs), which are themselves generated from human pluripotent stem cells. The method for generating midbrain immature neurons and mature neurons uses a chemically defined medium that enables the generation of mature dopaminergic neurons in just 23 days. Media, isolated cell populations, and kits are also provided.

The present invention belongs to the technical field of traditional Chinese medicine, and specifically discloses a use of a traditional Chinese medicine composition in preparing a drug for preventing or treating neurodegenerative diseases. The traditional Chinese medicine composition is made of leeches, chuanxiong, salvia miltiorrhiza and astragalus, has the effects of promoting blood circulation and removing blood stasis, invigorating qi and unblocking collaterals, and can effectively improve general behavioral performance, enhance balance and coordination ability and autonomous activity ability, reduce bradykinesia symptoms, relieve anxiety, and significantly increase substantia nigra TH + The invention discloses a novel Chinese medicine composition for treating Parkinson's disease, which can reduce or delay the loss of dopaminergic neurons in the midbrain, has a neuroprotective effect, and has no liver or kidney damage. It has a significant effect on the treatment of Parkinson's disease and is a safe and effective Chinese medicine composition for the treatment of Parkinson's disease, and has a good prospect for promotion and application.

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.

The present application provides methods for generating human midbrain immature neurons and mature dopaminergic neurons from neural progenitor cells. In some embodiments, immature and mature midbrain neurons are obtained from neural progenitor cells, such as targeted midbrain neural stem cells (NSCs) and midbrain neural progenitor cells (midbrain NPCs), while they themselves are generated from human pluripotent stem cells. Methods for generating immature and mature neurons of the midbrain use a chemically defined medium that allows for the generation of mature dopaminergic neurons within a short of 23 days. Media, isolated cell populations, and kits are also provided.

The present invention relates to the use of a culture medium-based method for inducing the specific differentiation of dental stem cells into dopaminergic neurons. The purpose of the present invention is to develop cell applications for treating degenerative neurological diseases and drugs related to the diseases.

The application belongs to the technical field of medicine and the technical field of brain degenerative diseases, and particularly relates to application of a PHGDH inhibitor NCT-503 in preparation of a medicine for preventing and treating Parkinson's disease, and verifies that specific inhibition of PHGDH can inhibit nerve inflammation in the brain substantia nigra region in vivo, reduce death of dopaminergic neurons, and thus relieve occurrence and development of Parkinson's disease; acute Parkinson's disease model mice are constructed by intraperitoneal injection of MPTP, and it is found that intraperitoneal injection treatment of NCT-503 can effectively reduce MPTP-induced nerve inflammation and reduce death of dopaminergic neurons. In conclusion, it is found for the first time that use of NCT-503 to inhibit PHGDH activity can significantly inhibit MPTP-induced nerve inflammation and reduce death of dopaminergic neurons, which provides an important theoretical basis for clinical application of NCT-503, and also provides a new idea for medicine research and development and screening 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.