43 results about "Notch signalling pathway" patented technology

The present invention is directed to methods of treating or preventing atherosclerosis and other cardiovascular diseases by administering agents that inhibit or modulate the NOTCH signaling pathway. In addition, the invention encompasses methods for assaying compounds for their ability to treat atherosclerosis based upon their effects on NOTCH signaling, and for measuring levels of amount, function, or activity of NOTCH pathway components in biological samples.

The regenerative potential of aged stem cells is enhanced by activation of the Notch signaling pathway and / or inhibition of TGF-β signaling pathway. Stem cells in aged tissues are capable of proliferation and tissue regeneration, but in their native setting are not provided with the appropriate signals to do so. By administering tissue regenerating agents, organ stem / progenitor cells are provided with the appropriate signals to regenerate the corresponding differentiated tissues.

The present invention is directed to methods of treating or preventing a metabolic disease or disorder and cardiovascular complications and other complications thereof by administering agents that inhibit the NOTCH signaling pathway. In addition, the invention encompasses methods for determining whether a patient is at increased risk for developing these conditions by determining the amount, function, or activity of NOTCH pathway components in biological samples derived from the patient or in imaging analyses.

Methods and compositions are provided for treating an individual having cancer. Aspects of the methods include administering to the individual an inhibitor of a non-canonical Notch signaling pathway gene in an amount effective to treat the cancer. Also provided are reagents, devices and kits thereof that find use in practicing the subject methods.

The present invention is based on the discovery that the Notch signaling pathway is associated with cancer. Accordingly, the invention provides methods and compositions for treating cancer. Also provided are methods of modulating the expression and / or activity of proteins in the Notch signaling pathway for use in diagnoses and treatment of cancer in a subject.

The present invention provides a method for directing differentiation of neural progenitors with a caudal and ventral specification into motor neurons comprising culturing neural progenitors in a culturing medium comprising a basic medium supplemented by at least one inhibitor of the Notch signaling pathway whereby said neural progenitors differentiate into postmitotic motor neurons. The resulting motor neurons may be used for drug development, as carriers, e.g. for gene therapy of protein delivery as well as for transplantation for the purpose of treating a motor neuron disease.

The regenerative potential of aged stem cells is enhanced by activation of the Notch signaling pathway and / or inhibition of TGF-β signaling pathway. Stem cells in aged tissues are capable of proliferation and tissue regeneration, but in their native setting are not provided with the appropriate signals to do so. By administering tissue regenerating agents, organ stem / progenitor cells are provided with the appropriate signals to regenerate the corresponding differentiated tissues.

The present invention provides methods of treating a disease or disorder, in which increasing the number of regulatory T cell (Treg) is beneficial, by administering to a subject suffering from such a disease or disorder a therapeutically effective amount of DII4 antagonists that block DII4-Notch signal pathways, thereby increasing the number of Treg. Diseases or disorders treatable by the methods of the invention include autoimmune diseases or disorders, such as multiple sclerosis (MS), diabetes, and the like. Suitable DII4 antagonists for the invention include antibodies or antibody fragments that specifically bind DII4 and block DII4-Notch interactions, the extracellular domain of DII4, and the like. The invention also provides methods of preventing an occurrence or recurrence of such diseases or disorders in a subject predisposed or susceptible to developing such diseases or disorders. Furthermore, the methods of the invention are useful in preventing or treating organ transplant rejections or graft-versus-host disease.

The present invention provides methods of preventing, treating or ameliorating diabetes by administering to a subject in need thereof a therapeutically effective amount of Dll4 antagonists that block Dll4-Notch signal pathways. As observed in a mouse model of diabetes, Dll4 antagonists exhibit protective effects on pancreatic islets, lower blood glucose levels, and block the production of auto-antibodies, including those against insulin and glutamic acid decarboxylase 65 (GAD65), via the expansion of regulatory T cells (Tregs). Thus, the present invention further provides methods of lowering the levels of blood glucose, and / or reducing or blocking the production of auto-antibodies, by administering to a subject in need thereof a therapeutically effective amount of Dll4 antagonists. Suitable Dll4 antagonists for the invention include antibodies or antibody fragments that specifically bind Dll4 and block Dll4-Notch interactions, the extracellular domain of Dll4, and the like.

The present invention provides methods of treating a disease or disorder, in which increasing the number of regulatory T cell (Treg) is beneficial, by administering to a subject suffering from such a disease or disorder a therapeutically effective amount of Dll4 antagonists that block Dll4-Notch signal pathways, thereby increasing the number of Treg. Diseases or disorders treatable by the methods of the invention include autoimmune diseases or disorders, such as multiple sclerosis (MS), diabetes, and the like. Suitable Dll4 antagonists for the invention include antibodies or antibody fragments that specifically bind Dll4 and block Dll4-Notch interactions, the extracellular domain of Dll4, and the like. The invention also provides methods of preventing an occurrence or recurrence of such diseases or disorders in a subject predisposed or susceptible to developing such diseases or disorders. Furthermore, the methods of the invention are useful in preventing or treating organ transplant rejections or graft-versus-host disease.

The present invention is based on the discovery that the Notch signaling pathway is associated with cancer. Accordingly, the invention provides methods and compositions for treating cancer. Also provided are methods of modulating the expression and / or activity of proteins in the Notch signaling pathway for use in diagnoses and treatment of cancer in a subject.

The present invention is directed to methods of treating or preventing atherosclerosis and other cardiovascular diseases by administering agents that inhibit or modulate the NOTCH signaling pathway. In addition, the invention encompasses methods for assaying compounds for their ability to treat atherosclerosis based upon their effects on NOTCH signaling, and for measuring levels of amount, function, or activity of NOTCH pathway components in biological samples.

Provided is a method for directing differentiation of neural progenitors with a caudal and ventral specification into motor neurons including culturing neural progenitors in a culturing medium including a basic medium supplemented by at least one inhibitor of the Notch signaling pathway whereby the neural progenitors differentiate into postmitotic motor neurons. The resulting motor neurons may be used for drug development, as carriers, e.g. for gene therapy of protein delivery as well as for transplantation for the purpose of treating a motor neuron disease.

Methods of generating spinal cord glutamatergic interneurons (V2a interneurons) from human pluripotent stem cells (hPSCs) are provided. A method of the present disclosure may include culturing a first population of hPSCs in vitro in a neural induction medium that includes: a retinoic acid signaling pathway activator; a sonic hedgehog (Shh) signaling pathway activator; and a Notch signaling pathway inhibitor, wherein the culturing results in generation of a second population of cultured cells containing CHX10+ V2a interneurons. Also provided are non-human animal models that include the hPSC-derived spinal cord glutamatergic interneurons, and methods of producing the non-human animal models.

The present invention relates to stem cells in which a gene that activates signaling is introduced and to a method for proliferating the stem cells. More specifically, the invention relates to a method of significantly increasing the ability of stem cells to proliferate, either by transfecting stem cells with the Notch intracellular domain (NICD) to activate the Notch signaling pathway, or by transfecting stem cells with the c-MET gene and treating the transfected stem cells with the HGF ligand protein to activate the c-MET / HGF signaling pathway. According to the present invention, as a result of activating the Notch signaling pathway or the c-MET / HGF signaling pathway, stem cells having an excellent ability to proliferate can be produced in large amounts. Particularly, since neural stem cells which have been difficult to culture in vitro can be proliferated in large amounts, thus the neural stem cells will be more useful for the preparation of cell therapeutic agents for treating cranial nerve diseases.

A method of constructing a zebrafish notch1a mutant using CRISPR / Cas9 technique. The method includes: determining a target for knocking out notch1a; using primers T7-notch1a-sfd and tracr rev for PCR amplification with a pUC19-gRNA scaffold plasmid as a template; transcribing PCR product in vitro followed by purification to obtain gRNA; and microinjecting the gRNA and a Cas9 mRNA into a zebrafish embryo followed by culture to obtain an notch1a mutant of stable inheritance. The invention selects a specific target and utilizes CRISPR / Cas9 technique to knock out the notch1a in the zebrafish without destroying other genes, generating the zebrafish notch1a mutant. Moreover, the invention also discloses the phenotype of the zebrafish notch1a mutant, which plays a significant role in studying the effect of the Notch1a receptor in the Notch signaling pathway.

A method for monitoring the immune system comprising monitoring the Notch signalling pathway.

The present invention is directed to methods of treating a patient to prevent vein graft failure by administering a compound that inhibits the Notch signaling pathway.

The invention discloses a blocking agent capable of inhibiting porcine reproductive and respiratory syndrome virus (PRRSV) infection. The invention discovers a new PRRSV cell target protein, namely Snf2-related CBP activator protein (SRCAP), and finds out inhibitory targets of the receptor. PRRSV infection can be significantly reduced by interfering SRCAP genes or using a Notch signaling pathway inhibitor, namely a gamma-secretase inhibitor, in which the SRCAP protein plays a key role at the inhibitory targets; and thus, the inhibitory targets and the gamma-secretase inhibitor can be developedinto drugs used for preventing and treating PRRSV infection, thereby providing brand new ideas for PRRSV research as well as prevention and treatment. Therefore, scope of research is expanded; and thus, the blocking agent is of great significance to practical production.

The invention provides application of a Notch signaling pathway inhibitor in preparation of drugs treating autism. Researches of the brain area of an autism animal model find that the Notch signalingpathway of the VPA autism model is more active and protein expression of NICD and downstream target molecule HES-1 is increased; meanwhile, the researches further find that application of DAPT reducesprotein expression of NICD and HES-1 and reduction of activity of the Notch signaling pathway can improve repeated, rigid behaviors of the autism animal model and increase the social contact abilityof the autism animal model so as to improve space learning and memory ability. The Notch signaling pathway inhibitor can reduce the activity of the Notch signaling pathway of an autism mouse model andimprove autism behavior abnormalities, thereby providing experimental basis and theoretical basis for research of drugs treating autism and clinical treatment of autism, and having excellent clinicaltreatment and drug research and development values.

A purification and renaturation method of Notch ligand Delta-like1 fusion protein is characterized by comprising steps as follows: 1), an inclusion body containing HD1R is repeatedly washed and centrifuged by a washing buffer and is dissolved in a strong denaturant buffer to obtain crudely separated HD1R protein; 2), a denatured leaching solution containing human proinsulin is subjected to direct sample introduction to a flowing phase A balanced chromatographic column and is subjected to isocratic elution by a flowing phase B line of PBS (poly butylenes succinate), 1 mol / L of NaCl or Tris and 1 mol / L of NaCl, target peak chromatographic fraction is collected, and renatured and purified HD1R chromatographic fraction is obtained; and 3), the collected target peak chromatographic fraction is subjected to direct sample introduction, is further desalinated by the flowing phase A balanced chromatographic column of 20 mmol / L of PBS and is continuously eluted for 30 min, the elution flow velocity is 0.5-1.5 ml / min, and the renatured and purified chromatographic fraction with higher purity and higher activity is obtained. According to the method, the process is simple, large-scale production can be realized, and the obtained fraction with high yield and high purity can provide a reliable experimental material for intensive study of Notch signal pathways.

The present invention relates to stem cells in which a gene that activates signaling is introduced and to a method for proliferating the stem cells. More specifically, the invention relates to a method of significantly increasing the ability of stem cells to proliferate, either by transfecting stem cells with the Notch intracellular domain (NICD) to activate the Notch signaling pathway, or by transfecting stem cells with the c-MET gene and treating the transfected stem cells with the HGF ligand protein to activate the c-MET / HGF signaling pathway. According to the present invention, as a result of activating the Notch signaling pathway or the c-MET / HGF signaling pathway, stem cells having an excellent ability to proliferate can be produced in large amounts. Particularly, since neural stem cells which have been difficult to culture in vitro can be proliferated in large amounts, thus the neural stem cells will be more useful for the preparation of cell therapeutic agents for treating cranial nerve diseases.

The present invention is directed to methods of treating a patient to prevent vein graft failure by administering a compound that inhibits the Notch signaling pathway.

The invention relates to a culture solution for preparing pancreatic beta cells by inducing directional differentiation of pluripotent stem cells, the culture solution comprises an AdvancedDMEM / F12 culture medium, glucose, sodium bicarbonate, human serum albumin (HSA), N2, B27, glutamine, vitamin C, a JNK inhibitor, a hedgehog pathway antagonist, EGF signal factors, FGF signal factors, a TGF-beta inhibitor, a WNT signal pathway activator, a Notch signal pathway inhibitor, a small molecule compound and trace elements, the ratios of the culture solution in different stages of cell culture are different, all the components play roles directionally in stages, and the pluripotent stem cells can be efficiently induced to be directionally differentiated into the pancreatic beta cells.