190 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 provides a cheese protein hydrolysate as well as a preparation method and application thereof. The composition of the casein hydrolysate at least comprises at least one of a peptide fragment 1 with an amino acid sequence as shown in SEQ ID NO: 1, a peptide fragment 2 with an amino acid sequence as shown in SEQ ID NO: 2 and a peptide fragment 3 with an amino acid sequence as shown in SEQ ID NO: 3. The casein hydrolysate has good neuron protection and repair effects, and can improve cholinergic neuron and dopaminergic neuron damage; abeta protein deposition can be inhibited, so that neuronal synaptic disorder, neuronal apoptosis and brain injury caused by Abeta protein deposition are relieved; the cholinergic defect can be improved, so that the nerve development damage and the behavior and movement disorder caused by the cholinergic defect are relieved; and damaged neurons in hippocampus and hypothalamus can be repaired, so that the brain environment is kept stable.

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.

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 a sea cucumber peptide with an anti-PD (Parkinson's Disease) effect, a computer simulation screening method, a synthesis method and application thereof in treatment of Parkinson's Disease, belongs to the field of active peptide screening and application, and solves the problem that the screened and synthesized sea cucumber peptide has the anti-PD effect, and has the technical key points that the sea cucumber peptide is prepared, and the sea cucumber active peptide is screened and synthesized from the sea cucumber peptide. The amino acid sequence of the sea cucumber active peptide is Gln-Trp-Phe-Asp-Trp, and the sea cucumber active peptide mixture has the effects that the prepared sea cucumber active peptide mixture can improve the behavioral level of a mouse induced by Rot, reduce the loss of dopaminergic neurons of nigra, improve the survival rate of SH-SY5Y cells induced by the Rot and improve the survival rate of the SH-SY5Y cells induced by the Rot. The active sea cucumber peptide screened by computer simulation analysis and in-vitro activity experiments on the basis of peptidomics analysis can improve the behavioral level of Rot-induced juvenile zebrafish of 7-day-old zebrafish, alleviates the pathological process of PD by reducing the endogenous ROS content of Rot-induced SH-SY5Y cells and alleviating mitochondrial membrane potential damage, and has a relatively good anti-PD effect.

The invention relates to a genetically modified induced neural stem cell and an asynchronous co-culture method. By providing a CRISPR / Cas9 engineered Nurr1-driven dopamine energy report induced neural stem cell model, the differentiation of dopaminergic neural precursor cells and neurons can be monitored in real time, a key pathway related to differentiation heterogeneity is revealed through RNA sequencing, an asynchronous co-culture method is established, and the method has the advantages of simple operation, low cost and high efficiency. The yield and purity of the dopaminergic nerve precursor cells can be improved, and the dopaminergic nerve precursor cells are successfully transplanted and differentiated into dopaminergic neurons in mouse striatum to prove the treatment potential of the dopaminergic nerve precursor cells for Parkinson's disease.

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.

Disclosed herein are formulations containing carbidopa and optionally levodopa, arginine, and other components that have reduced levels of impurities and toxins, particularly degradation productions. Also disclosed herein are methods of treatment diseases or conditions relating to a loss of dopamine or dopaminergic neurons using such formulations, methods of making such formulations, and kits that include such formulations.

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.