93 results about "Neurotrophin" patented technology

The invention relates to bifidobacterium breve CCFM1025, a fermented food and application thereof. The bifidobacterium breve CCFM1025 can be used for improving the depression-like behavior of a depression mouse, improving 5-hydroxytryptamine in the brain of the depression mouse, improving the level of 5-hydroxytryptamine and a brain-derived neurotrophic factor, reducing the level of corticosteronein serum of the depression mouse, improving the level of 5-hydroxytryptamine in the serum of the depression mouse, improving intestinal flora disturbance of the depression mouse, reducing the abundance of intestinal veillonella, improving the abundance of bifidobacterium and mycoplasmataceae, improving alpha-diversity of intestinal flora and reducing occurrence of inflammatory bowel disease and obesity. By adopting the bifidobacterium breve CCFM1025, the mRNA level of tryptophan hydroxylase in a simulated entero-chromaffin cell can be improved, the secretion volume of 5-hydroxytryptophane ofthe cell can be improved, and a precursor substance is specifically provided to synthesis of 5-hydroxytryptamine in the brain. The bifidobacterium breve CCFM1025 has a wide application prospect.

Pantropic neurotrophic factors which have multiple neurotrophic specificities are provided. The pantropic neurotrophic factors of the present invention are useful in the treatment of neuronal disorders. Nucleic acids and expression vectors encoding the pantropic neurotrophins are also provided.

The present invention relates to glial cell line-derived neurotrophic factor (GDNF), a potent neurotrophin that exhibits a broad spectrum of biological activities on a variety of cell types from both the central and peripheral nervous systems. The present invention involves the cloning and characterization of receptors for GDNF. Nucleic acid and amino acid sequences are described for GDNFR protein products. A hydrophobic domain with the features of a signal peptide is found at the amino terminus, while a second hydrophobic domain at the carboxy terminus is involved in the linkage of the receptor to the cell membrane. The lack of a transmembrane domain and cytoplasmic region indicates that GDNFR requires one or more accessory molecules in order to mediate transmembrane signaling. GDNFR mRNA is widely distributed in both nervous system and non-neural tissues, consistent with the similar distribution found for GDNF.

The present invention pertains to the field of genomics and nanotechnology, specifically to the in vivo gene expression technologies and their application in gene therapy. It consists of the performance of the NTS-polyplex nanocomplex, which can carry nucleic acids to the neurons, involving neurotrophic therapy to treat neurodegenerative diseases. In particular, the present invention addresses the treatment of Parkinson's disease by the regulated expression of the BDNF neurotrophin.

This invention pertains to the discovery that brain-derived neurotrophic factor (BDNF) and its associated signaling pathway is involved in reversing and/or counteracting neuroadaptations within the mesolimbic system that contribute to the development and/or maintenance of addiction (e.g. alcohol addiction). This invention also pertains to the discovery that ibogaine activity is mediated by changes in mRNA expression of GDNF. Thus, in certain embodiments, this inventioni provides a method of mitigating one or more symptoms of substance abuse in a mammal by increasing the expression or activity of GDNF, BDNF, RACK1, and/or the dopamine D3 receptor (D3R) in said mammal.

The invention relates to a mesenchymal stem cell of marrow, umbilical cord or bleeding of the umbilicus and purpose in the field of cell transplantation, stem cell culture, expansion and oriented differentiation. The mesenchymal stem cell for expressing a related gene of a neurotrophin family is prepared by the following steps of extracting a mesenchymal stem cell from the marrow, the umbilical cord or the bleeding of the umbilicus; recombining the related gene of the neurotrophin family to an AAV (Adeno-Associated Virus) used as a carrier; preparing the AAV expressing the related gene of the neurotrophin family; and infecting separated and purified mesenchymal stem cell through AAV particles to obtain the mesenchymal stem cell expressing the related gene of the neurotrophin family. The invention is used as a culture layer cell to provide a manually controlled microenvironment for stem cell culture, expansion and oriented differentiation and promote the proliferation and the oriented differentiation of the stem cells so as to provide a new curing measure for human diseases.

The invention relates to a biotechnology and especially relates to a construction method of a glial cell line-derived neurotrophic factor gene-modified embryo neural stem cell. The construction method comprises the following steps of 1, plasmid transformation, 2, plasmid digestion purification, 3, target gene and vector cloning, 4, recombinant plasmid packaging, 5, recombinant plasmid identification, 6, virus titer determination, 7, stem cell culture, 8, virus infection of the stem cells, 9, transgenic stem cell identification, 10, transgenic stem cell target-protein content determination, and 11, transgenic stem cell biological-activity detection. The glial cell line-derived neurotrophic factor gene-modified embryo neural stem cell has strong effects of promoting survival of dopaminergic neurons and retains characteristics of the original neural stem cell. The glial cell line-derived neurotrophic factor gene-modified embryo neural stem cell has good effects of treating motor neuron damage diseases and neuronal degeneration diseases.

The invention discloses nanoparticles loaded with therapeutic factors or neurotrophic factors. The nanoparticles are made of a high molecular material; the high molecular material is composed of biocompatible positively charged epsilon-polylysine and negatively charged heparin; the mass ratio of epsilon-polylysine to heparin ranges from 1:20 to 1:1; and average particle size grain diameter of the nanoparticles ranges from 100 to 400nm. The epsilon-polylysine-heparin nanoparticles are taken as carriers for loading of neurotrophic factors, and are high in biocompatibility, and stable in biochemical properties. The nanoparticles loaded with neurotrophic factors are capable of promoting cell axon growth effectively via sustained release.

An agent selected from A/B-cis furostane, furostene, spirostane and spirostene steroidal sapogenins and ester, ether, ketone and glycosylated forms thereof is used to induce self-regulated homeostasis of neurotrophic factors (NFs), for example BDNF and/or GDNF, NFs with limited and manageable side effects in a subject, by modulating NFs in a non-toxic manner under homeostatic control. An effective amount of at least one such agent is administered to the subject, particularly in the treatment or prevention of a range of NF-mediated disorders, particularly neurological, psychiatric, inflammatory, allergic, immune and neoplastic disorders, and in the restoration or normalisation of neuronal and other function in or in relation to any damaged or abnormal tissue, including when assisting tissue (for example, skin, bone, eye and muscle) healing and general skin, bone, eye and muscle health.

Methods and kits are provided for manipulating and predicting the reproductive capacity of a female subject. The presence of endogenous neurotrophins and addition of exogenous neurotrophins, particularly BDNF, NT-4/5, and NGF, increase the reproductive capacity of a female patient by binding to receptors on the oocytes and stimulating maturation of the oocytes. Administration of antagonists act as a contraceptive because the antagonists prevent the neurotrophins from binding to oocyte receptors. Neurotrophins may also be used to stimulate the maturation of oocyte in vitro.

The invention relates to bioengineering technologies, and particularly relates a method of inducing differentiation of neural stem cells into dopaminergic neurons by using recombinant slow virus. The method comprises the following steps: constructing a recombinant slow virus vector; separating, culturing and identifying the neural stem cells; transfecting the recombinant slow virus into NSCs; identifying the NSCs transfected by the recombinant slow virus, wherein the process of transfecting the recombinant slow virus into the NSCs comprises the following steps: digesting NSCs after being subjected to three times of passages to prepare a single-cell suspension, and inoculating into a culture plate; transfecting the TH+Brn4 gene recombinant slow virus; adding the slow virus and ploybrene, uniformly shaking, putting the culture plate into an incubator to culture for 1-2 hours, and replacing fresh differential culture medium; meanwhile, screening by using puromycin to obtain stable transfected cells. The method has the advantages as follows: by constructing the slow virus vectors of target genes TH and Brn4, exogenous genes after transfecting the NSCs can be stably expressed in cells; high proportion of TH positive dopaminergic neuron is generated after differentiation; the Brn4 can promote high expression of neurotrophic factors and has the function of inhibiting apoptosis.

Neurotrophin binding to its specific receptors Trk A and p75 leads to the activation of multiple signalling cascades, culminating in neuroprotective and regenerative effects, including neuronal survival and neurite outgrowth. Neurotrophic factors have been used for the treatment of several neurodegenerative diseases. However, their use is limited by their inability to cross the blood-brain barrier, their short half life and their side effects. Small molecule neurotrophin mimetics may be beneficial in treating a number of neurodegenerative disorders. The present invention shows the capacity of nerve growth factor agonist molecules of Formulae I-IV, as defined in the specification, to induce differentiation in PC 12 cells, promote survival in RN22 cells and activate Trk A, IkBa and SAPK/JNK phosphorylation to various extents in both cell lines. In addition these molecules were able to ameliorate acute experimental autoimmune encephalomyelitis (EAE), a multiple sclerosis (MS) animal model, inhibiting brain inflammation and reducing brain damage. We also observed suppression in the production of pro-inflammatory genes like the inducible nitric oxide synthase. These small molecules with NGF agonist activity may be beneficial for MS and other neurodegenerative diseases due to its neuroprotective and immunomodulatory properties.

The present invention discloses a clone of a neurotrophic factor fusion protein gene containing a protein transduction domain, the expression and the purification of the protein, the biological activity of the fusion protein, and the effect for penetrating a cell membrane, particularly for the blood-brain barrier in vivo. The fusion protein comprises a first area which has at least 75 percent of a homologous sequence with a neurotrophic factor and a second area which has at least 75 percent of a homologous sequence with an amino acid sequence of the protein transduction domain, and the second area is positioned at a carboxyl-terminal of the first area; the present invention can carry out the replacement, deletion or addition of the amino acid residues under the premise of not changing the characteristics of the fusion protein. The fusion protein can be used as a drug for the treatment of a plurality of neurodegenerative disorders in central nervous system and the peripheral neuropathies by peripheral routes for drug delivery.

A specific clinical protocol for use toward therapy of defective, diseased and damaged cholinergic neurons in the mammalian brain, of particular usefulness for treatment of neurodegenerative conditions such as Alzheimer's disease. The protocol is practiced by delivering a definite concentration of recombinant neurotrophin into, or within close proximity of, identified defective, diseased or damaged brain cells. Using a viral vector, the concentration of neurotrophin delivered as part of a neurotrophic composition varies from 10¹⁰ to 10¹⁵ neurotrophin encoding viral particles/ml of composition fluid. Each delivery site receives form 2.5 μl to 25 μl of neurotrophic composition, delivered slowly, as in over a period of time ranging upwards of 10 minutes/delivery site. Each delivery site is at, or within 500 μm of, a targeted cell, and no more than about 10 mm from another delivery site. Stable in situ neurotrophin expression can be achieved for 12 months, or longer.

The present disclosure provides a method of deriving and maintaining a midbrain-like organoid in culture, comprising (a) culturing pluripotent stem cells to obtain neuronal lineage embryoid bodies; (b) culturing the neuronal lineage embryoid bodies from (a) to obtain midbrain regionalized tissues; (c) embedding and culturing the midbrain regionalized tissues from (b) in an extracellular matrix to obtain neuroepithelial tissues; and (c) culturing the neuroepithelial tissues from (c) to obtain a midbrain-like organoid. Also disclosed herein are culture media suitable for deriving and maintaining neuronal lineage embryoid bodies comprising (a) TGF-β Inhibitor and/or SMAD2/3 inhibitors; and (b) WNT-signaling activator; culture media suitable for deriving and maintaining midbrain regionalized tissues comprising (a) TGF-β Inhibitor and/or SMAD2/3 inhibitors; (b) WNT-signaling activator; (c) hedgehog signaling protein; and (d) fibroblast growth factor; culture media suitable for deriving and maintaining neuroepithelial tissues comprising (a) hedgehog signaling protein; and (b) fibroblast growth factor and culture media suitable for deriving and maintaining a midbrain-like organoid comprising (a) neurotrophin factor; (b) ascorbic acid; and (c) activator of cAMP-dependent pathway.

The present invention discloses the production process of neurotrophic factor. The production process includes computer-aided design, modifying and altering the gene of ciliary nerve trophic factor to obtain modified mutation human ciliary nerve trophic factor cDNA, artificially synthesizing the cDNA, constituting recombinant plasmid, converting to bacillus coli, high density expression in automatic fermentation tank; renaturation in tangent flow superfiltering mode; ion exchange chromatography, hydrophobic chromatography and molecular sieve chromatography to purify and thus to obtain high-purity ciliary nerve trophic factor. The present invention has the advantages of stable and efficient expression of mutant in bacillus coli, less polarization insuperfiltering course and high purity of renaturated ciliary nerve trophic factor.

Disclosed is a method for inhibition of necrosis induced by neurotrophin, and more specifically a method for inhibition of necrosis by administrating oxidative stress inhibitor and a method for simultaneous inhibition of necrosis and apoptosis by administrating oxidative stress inhibitor and neurotrophin. The oxidative stress inhibitor of the present invention can inhibit nerve cell necrosis induced by neurotrophin. Moreover, it can be used for protecting nerve cell damage connected with alzheimer disease, parkinson's disease, degenerating cerebropathia and promoting regeneration of the nerve cells by administrating oxidative stress inhibitor and neurotrophin.

The invention discloses a method for promoting mesenchymal stem cells to differentiate into neurons, comprising the following steps: 1) preparing human mesenchymal stem cells and subculturing; 2) differentiating the passaged human mesenchymal stem cells into human mesenchymal stem cells in a differentiation medium-neurosphere; 3) differentiating the human mesenchymal stem cell-neurosphere into neurons in an induction culture medium. Neurotrophic factors are added to the induction culture medium to promote the differentiation into neurons, and the results show that expressing mature nerve marker (MAP2ab) and immature nerve marker (beta-tubulin III) were significantly improved relative to the blank control. The method of the invention provides a certain direction for a new treatment method for promoting the repair of spinal cord injury.

The invention discloses a culture method for promoting proliferation and differentiation of neural stem cells. According to the culture method, exogenous neurotrophic factors act to the cultured neural stem cells, so that the neural stem cells are induced to have proliferation and differentiation, and then neurons are formed, wherein the exogenous neurotrophic factors belong to a polypeptide with the sequence shown as SEQ ID NO.1; the exogenous neurotrophic factors and enhanced peptide act to the cultured neural stem cells together, so that the neural stem cells are induced to have proliferation and differentiation, and then neurons are formed, wherein the enhanced peptide is an oligopeptide with the sequence shown as SEQ ID NO.2, SEQ ID NO.3 or SEQ ID NO.4. According to the method provided by the invention, by supplementing the exogenous neurotrophic factors, the proliferation of neural stem cells and the differentiation of the neural stem cells towards the neurons can be obviously promoted, the enhanced peptide can enhance the effects of promoting proliferation and inducing differentiation of the exogenous neurotrophic factors, and the effects are obvious.

The invention belongs to the technical field of stem cells and particularly relates to umbilical cord mesenchymal stem cells modified by NTF4 (neurotrophin 4) gene and a construction method and application thereof. The umbilical cord mesenchymal stem cells modified by NTF4 gene are provided herein and can overexpress NTF4 protein. The umbilical cord mesenchymal stem cells modified by NTF4 gene canreplace damaged nerve cells, can well express NTF4 protein to arrive at nerve cell protection and promote cell regeneration and restoration, can be a treatment carrier having great potential of targeting therapy for cerebral arterial thrombosis, and can gain enhanced action of hUC-MSCs so that powerful combination is achieved. Experimental results show that the umbilical cord mesenchymal stem cells modified by NTF4 gene can be applied to model rats with focal cerebral ischemia to effectively repair brain damage of the rats.