45 results about "MPTP" patented technology

The application relates to the medical technical field, in particular to application of neoline in treatment of Parkinson's disease. 19 The C 19 The type-II diterpene alkaloid neoline can significantly improve movement disorder in a MPTP-induced Parkinson's disease model mouse, the drug efficacy is equivalent to that of the positive drug madopar, the effective dose is much lower than that of the positive drug, the administration mode is oral administration, drug compliance and use convenience are good, and the neoline can be used for development of anti-Parkinson's disease drugs.

The application discloses application of skin precursor cell induced Schwann cell derived vesicles (SKP-SC-EVs) in preparation of a product for treating Parkinson's disease, wherein the SKP-SC-EVs have a protective effect in rotenone or MPP+-induced cell injury, and in a MPTP-induced mouse Parkinson's disease model, the SKP-SC-EVs can be given by a nasal instillation method to improve the motor ability of the mouse and restore the olfactory function, and the product can be used for research and treatment of Parkinson's disease.

The present invention relates to a mitochondrial permeability transition pore (mPTP)-targeting composition for treating hearing loss, and, more specifically, uses a compound, or a pharmaceutically / sitologically acceptable salt thereof, which targets the mitochondrial permeability transition pore (mPTP) to inhibit the activity or opening thereof, and thus can effectively prevent, alleviate, or treat hearing loss caused by mPTP opening.

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

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

The application 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.

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 invention discloses an NDUFS2 gene heterozygous editing pig as well as a construction method and application thereof, and relates to the field of animal gene engineering and disease model construction. The eighth exon of the NDUFS2 gene of the pig is deleted or mutated, and presents an NDUFS2 heterozygous genotype; in the newborn period, the number of neurons of the middle cerebral cortical layer and the number of dopaminergic neurons are obviously reduced, the number of neurons of the adult cortical layer is continuously reduced along with mitochondrial swelling and crest fracture, and after MPTP treatment, the number of neurons of the adult cortical layer is disordered in motion trail, and the body tremor index is increased. The pig model not only can be used for revealing the action mechanism of the NDUFS2 defect in neurodegenerative diseases (such as Parkinson's disease), but also can be used as an important tool for screening new drugs, evaluating treatment means and researching mitochondrial diseases.

The application discloses a Parkinson's disease model animal, a method for establishing the Parkinson's disease model animal, and application of the Parkinson's disease model animal. In the Parkinson's disease model animal, a mouse Citrobacter rodentium (C.R) and / or a dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3.6-tetrahydropyridine (MPTP) is given to the animal. The phenotype of the Parkinson's disease model animal is stable, and the Parkinson's disease model animal can be used for researching the pathology of Parkinson's disease and screening and developing a therapeutic drug for Parkinson's disease caused by intestinal infection.

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

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.

The invention relates to the technical field of medicines, in particular to application of songorine in treatment of Parkinson's disease. The C20-type diterpenoid alkaloid songnin provided by the invention can obviously and continuously improve dyskinesia caused by dopaminergic neuron injury in MPTP-induced Parkinson's disease model mice, and the onset dose of songnin is obviously lower than that of clinically common positive medicine, namely medoxolane, so that the songnin shows a stronger drug effect and can be used for preparing drugs for treating Parkinson's disease. The compound can be developed into a novel efficient anti-Parkinson disease treatment medicine.

The invention discloses application of a miR-6809-5p inhibitor, and belongs to the technical field of biological medicine.The inventor finds that expression of miR-6809-5p in plasma of a PD patient is abnormally increased in the research of PD pathogenesis, and further cell experiments find that the expression of miR-6809-5p is abnormally increased in the plasma of the PD patient. By inhibiting the expression of the miR-6809-5p, the adverse effects of MPP + on cell viability, apoptosis, ROS, p-alpha-syn and TH protein can be effectively improved, and the miR-6809-5p has a remarkable treatment effect on PD. MPP + is an active metabolite of neurotoxin MPTP, can be selectively absorbed by dopaminergic neurons through dopamine transporter (DAT) protein to trigger degeneration death of the dopaminergic neurons, and is widely applied to construction of PD cell models to research pathogenesis of PD and drug evaluation. The miR-6809-5p inhibitor disclosed by the invention is used for preparing a medicine for treating the Parkinson's disease, and the nucleotide sequence of the miR-6809-5p inhibitor is as follows: UGAUCCUUUCUUUCCUUGCCA.

The invention discloses a composition which is composed of notoginsenoside Rg1 and gastrodin, the composition is applied to preparation of drugs for treating neurodegenerative diseases, and experimental results show that the composition can significantly improve MPTP-induced zebrafish dyskinesia and brain tissue structure damage, shows a synergistic neuroprotective effect, and can be used for treating neurodegenerative diseases. The composition provided by the invention provides a new effective means for treatment of neurodegenerative diseases, and has important clinical application value and wide development prospect.

The invention belongs to the technical field of medicines, and particularly discloses application of sesamoside in a medicine with a neuroprotective effect on Parkinson's disease, which is specifically characterized in that alpha-Syn plasmids are transfected into mouse dopaminergic neuron MES23.5 cells to establish an alpha-Syn overexpressed PD cell model, and PD cells are intervened by adding the sesamoside. Results prove that the sesamoside can improve cell viability and reduce cytotoxicity by reducing mitochondrial damage of PD cells, and has a neuroprotective effect on PD damaged neurons; a PD mouse model is established by utilizing MPTP intraperitoneal injection, intervention is carried out through sesamoside intragastric administration, and a result proves that sesamoside can effectively improve the athletic ability of a PD mouse. The results show that the sesamoside can effectively play a neuroprotective role on PD and has a good clinical application prospect.

The invention discloses a screening method and application of activity and effective components of Duliang soft capsules for treating Parkinson's disease, and relates to the technical field of medicines. The method comprises the following steps: firstly, measuring the contents of nine chemical components of the Duliang soft capsule by using a high performance liquid chromatography; the method comprises the following steps: constructing an in-vitro Parkinson's disease model by utilizing MPTP to induce SH-SY5Y cell injury, determining proper modeling and administration concentrations, and screening out components with neuroprotective effects such as SENA and ISO; the research on pharmacokinetics and tissue distribution of the six chemical components in the Duliang soft capsule finds that the components are low in metabolism and distribution speed in a rat body, can penetrate through a blood brain barrier and are widely distributed in various tissues; six components contained in DL are proved to have a remarkable curative effect on PD, and the action mechanism of the six components is related to regulation and control of mitochondrial Bcl-2 and Bax cell apoptosis pathways. The screening method is comprehensive and systematic, provides an active ingredient basis for treatment of Parkinson's disease by the Duliang soft capsule, is beneficial to deep research on the treatment mechanism of the Duliang soft capsule, and promotes research and development of novel anti-Parkinson's disease drugs.

The present invention relates to compounds of formula (I): and related aspects. The compound is an mPTP inhibitor.

The application provides application of a hydroxy pentylbenzoic acid double ester compound L-NRB in treatment of Parkinson's disease. Animal model test proves that L-NRB can effectively improve the MPTP-induced Parkinson's disease mouse behavior index, increase the content of DA and its metabolites DOPAC and HVA in the brain, inhibit the loss of dopamine neurons in the substantia nigra and striatum, inhibit the expression of inflammatory factors and the activation of astrocytes and microglia in the substantia nigra; meanwhile, L-NRB can also inhibit the activity of MAO-B in the striatum. L-NRB has no toxic side effects in vivo and in vitro; has the advantages of high safety, small dosage, long-term stability and the like, and is suitable for further development for actual clinical treatment.

The invention relates to a construction method of a Parkinson-brain organ and application of the Parkinson-brain organ in Parkinson treatment drug screening. The invention discovers that the brain organ can be simply, conveniently and quickly induced to form a Parkinson-brain organ capable of being used for screening Parkinson treatment drugs by treating the brain organ with MPTP, and a basis is provided for quickly screening the Parkinson treatment drugs. According to the application, the obtained Parkinson-brain organ is applied to screening a proper therapeutic drug from reduced triterpenoids, a good effect of Schinensilactone M in treatment of Parkinson's disease is found, formation of alpha-synuclein oligomers is remarkably reduced, activation of microglial cells and release of related inflammatory factors are effectively inhibited, and the Schinensilactone M can be used for treating Parkinson's disease, so that the Schinensilactone M can be used for treating Parkinson's disease. A new compound selection with a novel structure and a unique action mechanism is provided for prevention and treatment of Parkinson's disease.

The invention relates to application of columbianol angelica acid ester in preparation of a medicine for preventing and treating Parkinson's disease, and relates to the technical field of biological medicine. According to the application disclosed by the invention, the columbianidin is used for preparing the medicine for preventing and treating the Parkinson's disease, mitochondria damage of cells of the Parkinson's disease can be alleviated, and oxidative stress damage can be reduced, so that the cell activity is increased, the cytotoxicity is reduced, neuron damage of the Parkinson's disease is reduced, and a protection effect is achieved in neuron damage; the motion symptoms of the Parkinson's disease are improved. The dihydroopisorcinol angelate plays a role in protecting neurotoxicity induced by MPTP and metabolite MPP + thereof, provides a new medicine and method for preventing and treating Parkinson's disease, can be applied to preparation of various neuroprotective medicines, and has a better application prospect.

The invention belongs to the technical field of medicines, and particularly relates to application of a Chinese knotweed rhizome and aloe bowel-relaxing capsule to preparation of a medicine for treating Parkinson's disease. The Chinese knotweed rhizome and aloe bowel-relaxing capsule can obviously improve the damage of nigra and striatum dopaminergic neurons of mice suffering from the Parkinson's disease complicated with depression caused by MPTP and CUMS, and inhibit the activation of microglia and astroglia cells; the traditional Chinese medicine composition not only can relieve motion symptoms of mice with Parkinson's disease, but also can remarkably improve non-motion symptoms including mental disorder of the mice with Parkinson's disease, and has a remarkable treatment effect on depression of Parkinson's disease.

The invention relates to an application of bifidobacterium animalis subsp. Lactis BLa80 in preparation of a preparation for improving Parkinson's disease. The bifidobacterium animalis subsp. Lactis BLa80 is a strain of the bifidobacterium animalis subsp. Lactis BLa80 with the preservation number of CGMCC (China General Microbiological Culture Collection Center) No.22547, and the strain of the bifidobacterium animalis subsp. Lactis BLa80 is a strain of the bifidobacterium animalis subsp. Lactis BLa80 with the preservation number of CGMCC No.22547. The brand new application of the BLa80 strain of the animal bifidobacterium subsp. Lactis is developed, namely the BLa80 strain is used for improving the Parkinson's disease, specifically, the BLa80 strain can weaken the cytotoxicity of 6-OHDA induced SH-SY5Y cells, relieve weight loss of MPTP induced subacute Parkinson's disease model mice, relieve dyskinesia of the mice and improve the Parkinson's disease. According to the present invention, the mice are subjected to the mouse striatum activation, such that the dopaminergic neuron is protected, the dopamine content in the mouse striatum is increased, the intestinal inflammation is relieved, the ratio of the thick-wall mycophylum to the bacteroides in the mouse intestinal flora is increased, the intestinal beneficial flora abundance is improved, and the intestinal flora diversity is increased;

The invention discloses an activated near-infrared two-region fluorescent probe. The activated near-infrared two-region fluorescent probe comprises a small molecular dye and rare earth nanoparticles, wherein the small molecule dye is an organic small molecule which specifically responds to HClO; the rare earth nanoparticles are of a NaYF4: Yb, Er, Ce-coated NaYF4: Nd core-shell structure, NaYF4: Yb, Er and Ce are taken as a core, and NaYF4: Nd is taken as a shell. According to the invention, the emission of the rare earth nanoparticles at 1550nm is effectively regulated and controlled by utilizing the specific reaction of the small molecule dye and HClO, and the near-infrared two-region fluorescent probe responding to HClO is successfully constructed. The activated near-infrared two-region fluorescent probe is high in signal-to-noise ratio and sensitivity, can be used for in-vitro and in-vivo specific detection of HClO and real-time tracking and monitoring, has the advantages of being large in penetration depth, high in biological safety and the like, further realizes near-infrared two-region biological imaging, can be used for monitoring fluctuation of the concentration of HClO in the brain of an MPTP-induced Parkinson mouse, and can be used for detecting the concentration of the HClO in the brain of the Parkinson mouse. And the treatment effects of various Parkinson's disease treatment drugs are evaluated.

The invention belongs to the technical field of medicines, and particularly relates to application of CARNS1 in Parkinson's disease (PD). The research finds that CARNS1 is highly expressed in striatum and nigra brain regions in C57BL / 6 mouse brains, is positioned in dopaminergic neurons in the nigra brain regions, and is down-regulated in MPTP and alpha-syn animal models and MPP + cell models; the nigra region CARNS1 knocks down and aggravates MPTP-induced dyskinesia and neurodegeneration, and the exogenous supplement carnosine can partially reverse phenotypes; the overexpression of the wild type CARNS1 can be used for relieving the neurodegeneration in MPTP and alpha-syn models. The invention clarifies the regulation role of CARNS1 in PD, provides a new perspective for understanding the pathogenesis of PD, and prompts that the CARNS1-carnosine metabolic axis may become an important target for intervening the pathological process of PD.

The invention belongs to the technical field of medicines, and particularly discloses an application of an iridoid compound in a Parkinson's disease neuroprotective medicine, which is specifically characterized in that an alpha-Syn plasmid is transfected into a mouse dopaminergic neuron MES23.5 cell to establish an alpha-Syn overexpressed PD cell model, and 8-O-acetyl shanzhiside methyl ester is added to intervene the PD cell. Results prove that 8-O-acetyl shanzhiside methyl ester can improve cell viability and reduce cytotoxicity by reducing mitochondrial damage of PD cells, and has a neuroprotective effect on PD damaged neurons; a PD mouse model is established by utilizing MPTP intraperitoneal injection, intervention is carried out through intragastric administration of 8-O-acetyl shanzhiside methyl ester, and a result proves that 8-O-acetyl shanzhiside methyl ester can effectively improve the athletic ability of a PD mouse. The results show that the 8-O-acetyl shanzhiside methyl ester can effectively play a neuroprotective role on PD, and has a good clinical application prospect.