44 results about "Nonneuronal cell" patented technology

The present invention relates to methods, systems, and kits for intoxicating cells, neuronal and non-neuronal cells, with a toxin or fragment thereof. This is done by subjecting toxin substrate and a lipid or polymeric carrier (e.g., DNA uptake facilitating agent) to one or more cells for use in cell based assays. In an aspect, the methods of the present invention allow for high throughput assays and, as such, for the evaluation of drug candidates.

Provided are safe, non-invasive, non-viral delivery methods for providing a nucleic acid into the neuronal and non-neuronal cells of the central nervous system (CNS) of a subject to protect neuronal and non-neuronal cells from ischemic or traumatic injury, wherein the nucleic acid encodes a therapeutic proteins, specifically providing rapid transient expression and widespread distribution for in vitro or in vivo applications. Further provided are methods for the intrathecal delivery to the cerebrospinal fluid (CSF) of a neuroprotective gene sequence, e.g., a heat shock protein (HSP), complexed with cationic lipid compositions to achieve such delivery, and the complexes used therein.

The invention provides compositions and in vivo, ex vivo and in vitro methods for trans-differentiation of or re-programming mammalian cells to functional neurons. In particular, the invention provides methods for engineering non-neuronal cells into neurons, including fully functional human neuronal cells, and methods for engineering non-neuronal cells into neurons, e.g., fully functional human neuronal cells, in the brain to treat a neurodegenerative disease. In alternative embodiments, the invention provides compositions comprising re-differentiated or re-programmed mammalian cells, such as human cells, of the invention. The invention also provides compositions and methods for direct reprogramming of cells to a second phenotype or differentiated phenotype, such as a neuron, including a fully functional human neuronal cell. The invention also provides formulations, products of manufacture, implants, artificial organs or tissues, or kits, comprising a trans-differentiated or re-programmed cell of the invention, e.g., a fully functional human neuronal cell.

The present invention provides methods of generating a neuronal cell from a differentiated non-neuronal cell by increasing the amount of a miR-124 microRNA, a MYT1L transcription factor, and a BRN2 transcription factor in the differentiated non-neuronal cell.

Provided herein is a method of reprogramming a non-neuronal cell to a neuron. Aspects of the present disclosure relate to using cell reprogramming agent suppresses the expression or activity of PTB toconvert a non-neuronal cell into a neuron. Also provided herein is a method of treating neurodegenerative disease by reprogramming non-neuronal cells in vivo to functional neurons.

The subject invention concerns materials and methods for conversion of non-neuronal cells into neurons. The subject invention also concerns methods for screening drugs and other compounds for activity in treating Alzheimer's disease using neuronal cells produced using the subject invention. The subject invention also concerns neuronal cells that have been produced using the methods of the invention. The subject invention also concerns methods for evaluating therapeutic treatment for efficacy in a person or animal having Alzheimer's disease or other neurodegenerative diseases. The subject invention also concerns methods of treating Alzheimer's disease or other neurodegenerative diseases or conditions in a person or animal.

Provided are safe, non-invasive, non-viral delivery methods for providing a nucleic acid into the neuronal and non-neuronal cells of the central nervous system (CNS) of a subject to protect neuronal and non-neuronal cells from ischemic or traumatic injury, wherein the nucleic acid encodes a therapeutic proteins, specifically providing rapid transient expression and widespread distribution for in vitro or in vivo applications. Further provided are methods for the intrathecal delivery to the cerebrospinal fluid (CSF) of a neuroprotective gene sequence, e.g., a heat shock protein (HSP), complexed with cationic lipid compositions to achieve such delivery, and the complexes used therein.

The present invention relates to diagnosis and monitoring of Alzheimer's disease in the live subject. More particularly, the invention relates to methods involving the measurement of differential gene expression in non-neuronal cells taken from human subjects suspected of having Alzheimer's disease wherein the genes to be measured are genes within the m TOR signalling pathway.

The subject matter of the present disclosure generally relates to techniques for neuromodulation of a tissue that include applying energy (e.g., ultrasound energy) into the tissue to cause altered activity at a synapse between a neuron and a non-neuronal cell.

The present invention relates to diagnosis and monitoring of Alzheimer's disease in the live subject. More particularly, the invention relates to methods involving the measurement of differential gene expression in non-neuronal cells taken from human subjects suspected of having Alzheimer's disease wherein the genes to be measured are genes within the m TOR signalling pathway.

An isolated polypeptide comprising an amino acid sequence selected from amino acids 506-582 of SV2A, wherein position 573 is N and is glycosylated, or amino acids 449-525 of SV2B, wherein position 516 is N and is glycosylated. The present invention also provides an antibody that binds specifically to the polypeptide, an isolated nucleic acid comprising a polynucleotide that encodes the polypeptide; a method for reducing BoNT / E toxicity in an animal; a method for identifying an agent that blocks or inhibits binding between BoNT / E and an SV2A or SV2B protein; a method for monitoring synaptic vesicle endo- or exocytosis, a method for specifically delivering a chemical entity to a cell which has a specific receptor to a BoNT toxin. Also provided are a chimeric toxin for targeting a proteolytic domain of a toxin to a cell, the chimeric toxin comprising a catalytic or proteolytic domain of the BoNT toxin, and a ligand or a fragment thereof for a non-BoNT receptor on the cell; a method for targeting a proteolytic domain of a BoNT toxin to a cell, an isolated non-neuronal cell comprising a BoNT toxin receptor; and a method for screening for an inhibitor of a BoNT toxin.

The present inventions relate to methods and compositions useful for improving the efficiency of inducing the generation of neurons from non-neuronal cell types, for example, by contacting the cell or cell culture medium with one or more agents which inhibit Activin and / or PLK1 signaling. Also disclosed are methods for promoting neuron survival, for example, by inhibiting Activin and / or PLK1 signaling, and methods for promoting the survival of intermediates in a cell differentiation pathway, for example, by inhibiting Activin and / or PLK1 signaling.

The subject invention concerns materials and methods for conversion of non-neuronal cells into neurons. The subject invention also concerns methods for screening drugs and other compounds for activity in treating Alzheimer's disease using neuronal cells produced using the subject invention. The subject invention also concerns neuronal cells that have been produced using the methods of the invention. The subject invention also concerns methods for evaluating therapeutic treatment for efficacy in a person or animal having Alzheimer's disease or other neurodegenerative diseases. The subject invention also concerns methods of treating Alzheimer's disease or other neurodegenerative diseases or conditions in a person or animal.

This present invention features methods and composition for the isolation and proliferation of neural crest stem cells (NCSCs) from embryonic tissues as well as from tissues from a post-natal mammal. According to this invention, NCSCs are capable of producing non-neuronal and neuronal cells under the appropriate conditions. The cells of the invention therefore provide an accessible source for autologous and heterologous transplantation into the central nervous system, the peripheral nervous system, as well as other damaged tissues.

The invention relates to a method for generating functional noradrenaline neurons through reprogramming. According to the method, a plurality of transcription factors are overexpressed in non-neuronalcells, and differentiated somatic cells are induced into functional noradrenaline neurons in vitro. The noradrenaline neurons generated by the method disclosed by the invention can survive after being transplanted into a body, and can be used for developing medicines for preventing, improving or treating various nervous system diseases.

The invention discloses a bionic three-dimensional nerve blood vessel unit direct contact co-culture system which at least comprises neurons, semipermeable membranes, three-dimensional cultured astrocytes, semipermeable membranes and vascular endothelial cells, the three-dimensional cultured astrocytes are attached to the non-vascular endothelial cell side of a semipermeable membrane-vascular endothelial cell complex, and the semipermeable membrane-vascular endothelial cell complex is attached to the non-vascular endothelial cell side of the semipermeable membrane-vascular endothelial cell complex. And the semi-permeable membrane is attached to the non-neuron cell side of the semi-permeable membrane-neuron complex to form a direct contact co-culture system of vascular endothelial cells, three-dimensional culture astrocytes and neurons. The invention further discloses a construction method of the bionic three-dimensional nerve blood vessel unit direct contact co-culture system. According to the bionic three-dimensional nerve and blood vessel unit direct contact co-culture system and the construction and culture method thereof provided by the invention, physiological functions of blood brain barrier, nutrition coupling, electrophysiological coupling and the like of the nerve and blood vessel unit in vivo can be comprehensively and effectively simulated.

A novel assay method suitable for screening of novel antipsychotics wherein the drugs may be selected based on the differential internalization of the 5-HT2A receptor in neuronal and non-neuronal cell lines effect for it to predict the extrapyramidal symptoms that may be induced by an antipsychotic without having to carry out in vivo experiments.

Disclosed are biomarkers for Parkinson's disease (PD), including idiopathic PD (idPD). The present invention relates generally to assays, kits, compositions, solid supports and methods that measure a decrease in the expression or function of PLA2g6(L) variant of PLA2g6 (PARK 14) gene in a sample from the subject, including non-neuronal cells as a biomarker for preclinical (prodromal) or early stage Parkinson's disease (PD) and idiopathic PD (idPD), as well as assays, kits, compositions and methods that can detect the functional consequences of decreased expression of PLA2g6(L), including decreased store operated Ca2+ entry (SOCE), deficit of Ca2+ in endoplasmic reticulum stores, and autophagic dysfunction in the cells obtained from the subjects in preclinical (prodromal) and early stage PD diagnosis and for monitoring Parkinson's Disease progression.

The subject matter of the present invention generally relates to techniques for neuromodulation of a tissue that include applying energy (e.g., ultrasound energy) into the tissue to cause altered activity at a synapse between a neuron and a non-neuronal cell.

A modification of the existing INSM1 promoter region has been discovered that incorporated DNA elements that silence expression of neuronal genes in non-neuronal cells and that has increased the effectiveness and safety of using the INSM1 promoter for tumor treatment. One modification was addition of one or two tandem copies of neuronal restrictive silencer elements (NRSEs) derived either from the mouse nicotinic acetylcholine receptor (nAChR) or the rat superior cervical ganglion 10 (SCG10) promoters. These NRSEs were placed in the expression construct either directly upstream or downstream of the INSM1 promoter sequence. The most effective expression construct was the nAChR NRSE element positioned downstream of the INSM1 promoter. This expression construct increased the tissue specificity of the INSM1 promoter without a significant decrease in its activity. In addition, the modified INSM1 promoter was placed into a viral vector, adenovirus 5. Constructs with an insulator element, the chicken HS4 β-globin insulator element, with the INSM1 promoter was shown to decrease the interference of the viral genome on its expression. Constructs have been made that do not decrease the INSM1 promoter activity but significantly augment the tumor specificity of the promoter. Linking the construct to a reporter gene allowed for detection of the placement of the viral vector, and this detection can be used for diagnosing or locating neuroendocrine tumors.

The subject matter of the present disclosure generally relates to techniques for neuromodulation of a tissue that include applying energy (e.g., ultrasound energy) into the tissue to cause altered activity at a synapse between a neuron and a non-neuronal cell. In one embodiment, the energy is applied to cause persistent effects as a result of repeated application of energy within a predefined treatment window.

An isolated polypeptide comprising an amino acid sequence selected from amino acids 506-582 of SV2A, wherein position 573 is N and is glycosylated, or amino acids 449-525 of SV2B, wherein position 516 is N and is glycosylated. The present invention also provides an antibody that binds specifically to the polypeptide, an isolated nucleic acid comprising a polynucleotide that encodes the polypeptide; a method for reducing BoNT / E toxicity in an animal; a method for identifying an agent that blocks or inhibits binding between BoNT / E and an SV2A or SV2B protein; a method for monitoring synaptic vesicle endo- or exocytosis, a method for specifically delivering a chemical entity to a cell which has a specific receptor to a BoNT toxin. Also provided are a chimeric toxin for targeting a proteolytic domain of a toxin to a cell, the chimeric toxin comprising a catalytic or proteolytic domain of the BoNT toxin, and a ligand or a fragment thereof for a non-BoNT receptor on the cell; a method for targeting a proteolytic domain of a BoNT toxin to a cell, an isolated non-neuronal cell comprising a BoNT toxin receptor; and a method for screening for an inhibitor of a BoNT toxin.

A method for assessment of neural function by establishing an analysis module is revealed. The first step of the method is to capture images of the cultured cells with a plurality of fluorescence labeling by a fluorescence microscopy system for image analysis. The cultured cells include neurons and non-neuronal cells. Then select neurons with neurites having fluorescence labeling and exclude non-neuronal cells according to an area and a fluorescence intensity of nucleus. Also calculate an area of the neuronal cell body, a length of the neurites and a number of processes and branches to verify outgrowth of the neurites of the neurons. Next calculate a number of synaptic puncta having fluorescence labeling on the area of the neurites having fluorescence labeling defined in Step 2 to verify formation of the synaptic puncta of the neurons for assessment of neural function.

The present invention relates to methods for enhancing the cellular uptake and clearance of soluble oligomeric Aβ peptide assemblies from the environment surrounding both neuronal and non-neuronal cells. Oligomeric Aβ peptide assembly uptake and clearance is achieved via an agent that enhances insulin receptor signaling. Such ADDL uptake enhancers represent effective anti-ADDL therapeutics for use in the therapeutic treatment and / or prophylactic treatment of diseases including Alzheimer's disease, Down's syndrome, and the like, in which compromised nerve cell function is linked to the formation and / or the activity of soluble oligomeric Aβ peptide assemblies, also known as ADDLs, and ADDL-related assemblies.

A modification of the existing INSM1 promoter region has been discovered that incorporated DNA elements that silence expression of neuronal genes in non-neuronal cells and that has increased the effectiveness and safety of using the INSM1 promoter for tumor treatment. One modification was addition of one or two tandem copies of neuronal restrictive silencer elements (NRSEs) derived either from the mouse nicotinic acetylcholine receptor (nAChR) or the rat superior cervical ganglion 10 (SCG10) promoters. These NRSEs were placed in the expression construct either directly upstream or downstream of the INSM1 promoter sequence. The most effective expression construct was the nAChR NRSE element positioned downstream of the INSM1 promoter. This expression construct increased the tissue specificity of the INSM1 promoter without a significant decrease in its activity. In addition, the modified INSM1 promoter was placed into a viral vector, adenovirus 5. Constructs with an insulator element, the chicken HS4 β-globin insulator element, with the INSM1 promoter was shown to decrease the interference of the viral genome on its expression. Constructs have been made that do not decrease the INSM1 promoter activity but significantly augment the tumor specificity of the promoter. Linking the construct to a reporter gene allowed for detection of the placement of the viral vector, and this detection can be used for diagnosing or locating neuroendocrine tumors.

Cocktails of chemical inducers of neuron-like properties (CINP) is provided, which includes cAMP agonists, neurogenic small molecules, glycogen synthase kinase inhibitors, TGFβ receptor inhibitors, and BET family bromodomain inhibitors and optionally, a selective inhibitor of ROCK or p38 MAPK. These cocktails are used in a method of inducing neuron-like properties in partially or completely differentiated non-neuronal cells. The method includes contacting cells of a first type (non-neuronal) with the CINPs for a sufficient period of time to result in reprogramming the cell into cells of a second type having neuron-like characteristics (CiNs). Isolated chemically induced neurons (CiNs) can be used in a number of applications, including but not limited to cell therapy.

The invention provides a cell co-cultivation method used in the analysis of synapse formation, comprising the following steps: adding subcultured non-neuronal cells, namely HEK293 T cells, to 24-well primary cultured neuronal cells in an in vitro environment Medium, mixed and cultured for more than 24 hours; PEI transfection method was used to transfect HEK293 T cells, and the exogenous genes transfected in each well were different, and the transfected HEK293 T cells overexpressed exogenous genes, Under these conditions, co-culture was carried out for more than 48 hours; the presynaptic marker protein synapsin was immunostained to determine whether a synaptic structure was formed in each well. The co-cultivation method provided by the present invention solves the deficiencies in the prior art. The method is simple and convenient to operate, relatively low in cost and short in time, can screen genes well and verify gene functions, and can be widely used in laboratories .