64 results about "GABAergic 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 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 preparation, sorting and application of LGE / CGE organoid and GABAergic neurons, and belongs to the field of brain organoid differentiation and GABAergic neurons. The preparation method of the LGE / CGE type organ comprises the following steps: S1, performing embryoid formation and initial culture on the 0th-4th day; s2, performing nerve induction and matrigel embedding on the 5th-11th day; s3, culturing the brain organoid on the 12th day to the 19th day; s4, dynamically culturing and screening the brain organoid on the 20th-35th day; and S5, carrying out differentiation and collection on LCOs of the LGE / CGE type organs after the 35th day. According to the method, the LGE / CGE organs containing the high-purity GABA energy neurons are obtained through differentiation from the brain organs for the first time, the high-purity LGE type GABA energy neurons and the high-purity CGE type GABA energy neurons are obtained through a specific sorting method, and the method has the deep application potential in the fields of disease model construction, medicine research and development and the like.

The invention discloses a composition for regulating sleep rhythm homeostasis as well as a preparation method and application thereof. The composition for regulating the sleep rhythm homeostasis is prepared from the following components in percentage by weight: 5 to 18 percent of polydextrose, 9 to 15 percent of galactooligosaccharide, 1 to 10 percent of inulin, 0.4 to 2 percent of gamma-aminobutyric acid, 0.8 to 2.2 percent of L-theanine, 0.1 to 3.5 percent of magnesium citrate, 2 to 21 percent of semen ziziphi spinosae extract, 1 to 10 percent of poria cocos extract, 0.5 to 2 percent of pericarpium citri reticulatae extract, 0.3 to 1 percent of liquorice root extract and 15 to 40 percent of maltodextrin. 5-18% of coconut oil powder MCTs, and 0.5-2% of a lily extract. According to the application, a magnesium MCTs shell-core structure is delivered by maltodextrin to form a mitochondrial piezoelectric engine so as to improve prebiotics, promote flora metabolism efficiency and energy supply feedback, activate intestinal pheochromophilic cells and improve SLC6A4 gene expression so as to improve synthesis of 5-hydroxytryptamine in the brain and activate GABA energy neurons; meanwhile, through the spina date seed and poria cocos quantum dots and a pericarpium citri reticulatae and liquorice pi-pi stacking network, the blood-brain barrier penetration rate is greatly increased, and hypothalamic CRH release is adjusted.

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 relates to the technical field of nerve cell marking and regulation and control, in particular to a nerve cell living body selective protein modification probe capable of penetrating a blood brain barrier and application of the nerve cell living body selective protein modification probe. The protein body part specifically targets a living glutamic acid energetic neuron cell membrane, the protein body part and / or a modified part thereof can regulate and control the function of the glutamic acid energetic neuron, and a coding sequence of the protein body part comprises a sequence as shown in SEQ ID NO: 1 or a sequence having at least 85% identity with the SEQ ID NO: 1. The protein modified probe provided by the invention provides a new feasible thought for developing in-vivo nerve cell selective markers and regulation tools which are non-gene transfection of blood brain barrier penetration, are high in biological safety, are more stable and are easy to obtain and have nerve cell specific type selectivity.

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.

A method and system for differentiating acute and chronic pain based on the functional state of specific neural circuits is proposed. This method utilizes in vivo two-photon / endoscopic calcium imaging and ex vivo brain slice patch-clamp techniques to longitudinally monitor the activity dynamics of neurons in the DRN and ZI brain regions during the acute and chronic phases of a neuropathic pain model. By extracting and analyzing calcium and electrophysiological signal parameter sets, distinguishing criteria are established: if the activity of 5-HTergic neurons in the DRN is specifically enhanced in the acute phase, the indication is acute pain; if the activity of GABAergic neurons in the ZI is specifically enhanced in the chronic phase, the indication is chronic pain. This invention achieves an objective and precise differentiation of the transition from acute to chronic pain at the level of specific neural circuits, providing a new strategy and tool for pain mechanism research and clinical diagnosis and treatment.

The invention relates to the technical field of sleep regulation and control, and discloses a method for regulating and controlling anxiety insomnia based on LPAG brain region GABAergic neurons, which takes the regulation effect of LPAG on sleep-awakening as an entry point, adopts in-vivo multichannel recording, EEG / EMG polysleep synchronous recording, photoelectrode recording and opto-genetics manipulation on a cell-loop level, and realizes the regulation and control of anxiety insomnia. The system analyzes the effect of the LPAG in sleep-awakening, and proves the regulation effect of the LPAG on anxiety sleep disorder.

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 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.

This invention belongs to the field of biomedicine and relates to a method for preparing a Kabuki syndrome brain organoid model and its application. This invention provides the application of GSK-3 inhibitors in the preparation of drugs for treating Kabuki syndrome. Currently existing Kabuki models include heterozygous mice, zebrafish, and 2D human cell models. However, the complexity of human brain development cannot be compared to animal models or single 2D cell models. In this invention, the inventors used CRISPR-CAS9 gene editing technology to knock out KMT2D and established a Kabuki syndrome brain organoid model using brain organoid technology. Studies have found that, compared to the wild type, the Kabuki syndrome brain organoid exhibits premature differentiation of excessive GABAergic neurons. Furthermore, by testing the dosage and time window of the small molecule chir99021, we found that this small molecule can restore the phenotype of abnormal neuronal differentiation in the Kabuki syndrome brain organoid. This discovery will provide new insights for the treatment of Kabuki syndrome.

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.

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 invention relates to methods and compositions for developing basal forebrain cholinergic neurons (BFCNs) from stem cells, and in particular, BFCNs having repaired electrophysiological defects relating to one or more mutations in PSEN2, and to the use of such BFCNs in cell-based therapies to treat Alzheimer's disease.

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 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 provides a plant-derived active polypeptide and application thereof in prevention or treatment of Parkinson's syndrome, and belongs to the technical field of polypeptide bioengineering. The amino acid sequence of the active polypeptide is MKGASSIMYALG, and the active polypeptide is prepared from Fuding white tea raw materials through a directional two-step enzymolysis process. According to the polypeptide, the damage of 6-OHDA induced BZ555 nematode dopaminergic neurons can be remarkably reduced, and the dyskinesia of Parkinson's syndrome model animals can be remarkably improved; meanwhile, the expression level of proinflammatory factors such as IL-1beta and IL-18 in serum of a model mouse can be lowered, the content of dopamine in a nigra area of brain tissue of the model mouse can be increased, and the activity of monoamine oxidase B can be reduced. The results show that the Fuding white tea-derived active polypeptide has exact prevention and treatment effects on Parkinson's syndrome, and has important development value and wide application prospects in the field of medicines.

This invention discloses the application of GRP94 protein as a drug delivery target in the construction of drug carriers for Parkinson's disease. GRP94 is highly upregulated on the cell membranes of dopaminergic neurons in the substantia nigra of Parkinson's disease cells, while its expression is extremely low on the surface of normal brain cells. The invention also discloses the application of GRP94 as a target in a targeted delivery system for anti-Parkinson's disease drugs. By targeting GRP94, the delivered anti-Parkinson's drug can efficiently penetrate the blood-brain barrier to reach the brain parenchyma, avoiding normal brain cells and specifically targeting dopaminergic neurons in the substantia nigra of Parkinson's disease cells, thus achieving targeted drug delivery for Parkinson's disease. This invention applies GRP94 as a target in the construction of drug carriers for Parkinson's disease and in the preparation of targeted delivery systems for anti-Parkinson's disease drugs. Compared to other target receptors that cross the blood-brain barrier for targeted brain delivery, targeting GRP94 more specifically targets dopaminergic neurons in the substantia nigra, avoiding drug accumulation and neurotoxicity in normal intracranial regions.

The invention provides a neural stem cell induced differentiation and clinical application method for intractable epilepsy, and relates to the technical field of biological medicine, the induced differentiation method comprises the following steps: S1, cell source and preparation: adopting induced pluripotent stem cells from a patient; s2, constructing an induced differentiation system, differentiating the induced pluripotent stem cells into GABA (gamma-aminobutyric acid) inhibitory interneurons, and differentiating the GABA inhibitory interneurons; s3, purifying and amplifying the cells, adopting immunomagnetic bead sorting, and purifying and enriching the cells expressing the GABA energy neuron marker; s4, cell quality control; according to the method, the autologous induced pluripotent stem cells of the patient are taken as a source, immunological rejection is avoided, the transplanting safety is improved, and moreover, the high-purity GABAergic neurons can more effectively supplement damaged inhibitory neurons in the brain of the epileptic and reconstruct the inhibition balance of a neural network, so that the epileptic seizure is more effectively controlled.

This invention discloses a method for inducing adipose-derived stem cells to differentiate into dopaminergic neurons, belonging to the field of biomedical technology. Through the isolation, passage culture, and induced transformation of adipose-derived stem cells, dopaminergic neurons are obtained. This method achieves the separation and culture of a large number of adipose-derived stem cells from autologous adipose tissue. By using two specific culture media to transform the adipose-derived stem cells into dopaminergic neurons, a safe and effective batch of stable dopaminergic neurons with a high differentiation rate can be obtained. Immunofluorescence and cell counting experiments show that the dopaminergic neuron conversion rate is 90.4±0.76, and the survival rate is 98.9±0.55. The average dopamine secretion of the transformed dopaminergic neurons, detected by a dopamine ELISA kit, is 450 pg / ml. Therefore, this invention confirms that the adipose-derived stem cell extraction and transformation steps provided by this invention are mild and stable, and the extracted cells are suitable for large-scale applications.

The invention discloses application of an Apob gene in preparation of drugs for relieving depression, and belongs to the technical field of biological medicines. According to the present invention, it is found that the APOB protein of the brain region of the DMS is overexpressed, and the APOB protein has the anti-depression effect; when the Apob gene in the GABA energy neuron of the dorsal medial striatum (DMS) is knocked out, the mouse is correspondingly irritable and susceptible, which indicates that the Apob gene has a positive effect in dealing with depression.

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.

The present application belongs to the technical field of biological medicine, and particularly relates to a pharmaceutical composition for treating Parkinson syndrome. Researches show that the Antarctic fish protein and the multi-domain derivative thereof have the functions of reducing PD pathology and protecting dopaminergic neurons.

Compositions and methods for treating Parkinson's disease are provided. The present specification provides compounds, compositions, uses, and methods for increasing cell viability of dopaminergic neurons or for preventing or treating the death of dopaminergic neurons. In certain embodiments, methods are provided for alleviating symptoms and / or preventing or treating Parkinson's disease in an individual in need thereof, the methods comprising increasing GDP-bound Rab1a (Rab1a GDP ), Rab1a GDP The method includes treating with one or more expressible nucleic acids encoding the compound of formula (I), or a combination thereof.

The invention provides an efficient and repeatable in-vitro differentiation protocol, and human pluripotent stem cells are differentiated into functional midbrain dopaminergic neurons by accurately controlling sequential activation of SHH and FGF8 signal pathways. The protocol comprises five key differentiation stages: neural precursor induction, midbrain mode establishment, midbrain dopaminergic precursor amplification, terminal differentiation and maturation. Experiments prove that after the midbrain dopaminergic neuron obtained by the method is transplanted into a Parkinson's disease model animal body, the survival rate exceeds 80%, and the midbrain dopaminergic neuron can be effectively integrated into a host neural network and improve dyskinesia. According to the differentiation scheme, the purity (gt; gt) of mDA neurons is remarkably improved; 85%) and functional maturity, and a reliable cell source is provided for cell replacement treatment of Parkinson's disease.

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.

The present invention relates to a method for modulating the effect of a botulinum neurotoxin composition, that is accelerating the onset of action and / or extending the duration of action and / or enhancing the intensity of action of a botulinum neurotoxin composition, comprising adding at least one postsynaptic inhibitor of cholinergic neuronal transmission to the botulinum neurotoxin composition. The invention also relates to compositions comprising at least one postsynaptic inhibitor of cholinergic neuronal transmission and a botulinum neurotoxin, and their uses for treating aesthetic or therapeutic conditions.

The application discloses application of CD73+NK cells in preparation of drugs for preventing or treating Parkinson. The applicant finds in the experiment that CD73 + The NK cells can prevent MPP+-induced dopaminergic neuron loss and glial inflammatory response of VM cells. However, CD73 + TGF-β1 and IL-10 secreted by the NK cells can prevent MPP+-induced dopaminergic neuron loss and glial inflammatory response of VM cells. + The NK cells do not significantly prevent MPP+-induced dopaminergic neuron loss in transwell co-culture with VM neurons. And it is proved that CD73 + The NK cells protect the dopaminergic neurons from MPP+ neurotoxicity through an intercellular contact mechanism, i.e. CD73-SIRPA interaction.