52 results about "Glutamatergic" patented technology

The present invention is directed to compounds that inhibit the glycine transporter GlyT1 and which are useful in the treatment of neurological and psychiatric disorders associated with glycinergic or glutamatergic neurotransmission dysfunction and diseases in which the glycine transporter GlyT1 is involved.

A compound with general formula Ifor treatment of various diseases of the central nervous system, in treatment of neuropsychiatric disorders related to imbalance of glutamatergic neurotransmitter system, ischemic damage of CNS, neurodegenerative changes and disorders of CNS, affective disorders, depression, PTSD and other diseases related to stress, anxiety, schizophrenia and psychotic disorders, pain, addictions, multiple sclerosis, epilepsy and gliomas.

The present invention is directed to morpholinyl piperidine compounds that inhibit the glycine transporter GlyT1 and which are useful in the treatment of neurological and psychiatric disorders associated with glycinergic or glutamatergic neurotransmission dysfunction and diseases in which the glycine transporter GlyT1 is involved.

The present invention is directed to azetidine compounds that inhibit the glycine transporter GlyT1 and which are useful in the treatment of neurological and psychiatric disorders associated with glycinergic or glutamatergic neurotransmission dysfunction and diseases in which the glycine transporter GlyT1 is involved.

The present invention is directed to cyclopropyl piperidine compounds that inhibit the glycine transporter GlyT1 and which are useful in the treatment of neurological and psychiatric disorders associated with glycinergic or glutamatergic neuro-transmission dysfunction and diseases in which the glycine transporter GlyT1 is involved.

Azabicyclic, azatricyclic and azaspirocyclic derivatives of aminocyclohexanes which are systemically-active as NMDA, 5HT3, and nicotinic receptor antagonists, pharmaceutical compositions comprising the same, method of preparation thereof, and method of treating CNS disorders which involve disturbances of glutamatergic, serotoninergic, and nicotinic transmission, treating immunomodulatory disorders, and antimalaria, antitrypanosomal, anti-Borna virus, anti-HSV and anti-Hepatitis C virus activity.

Methods to detect amyotrophic lateral sclerosis (ALS) or presymptomatic Alzheimer's disease (PSAD) using an indicator cell assay platform (iCAP) in a test subject are described. Specifically, the disclosure provides a method comprising contacting a biological fluid of said test subject with indicator cells and assessing said indicator cells for the level of expression of an exon of CKIgamma2 that encodes the C-terminal palmitoylated region of said CKIgamma2, to determine the probability that a test subject is afflicted with amyotrophic lateral sclerosis (ALS). Further disclosed are methods of using indicator cells that are pan neuronal populations of glutamatergic (and / or GABAergic) neurons to determine the probability of the presence of presymptomatic or symptomatic Alzheimer's disease (PSAD) in a test subject.

The present invention is directed to pyridyl, pyridazinyl, pyrimidinyl and pyrazinyl piperidine compounds that inhibit the glycine transporter GlyT1 and which are useful in the treatment of neurological and psychiatric disorders associated with glycinergic or glutamatergic neurotransmission dysfunction and diseases in which the glycine transporter GlyT1 is involved.

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 the treatment or prevention of glutamatergic toxicity by the administration of effective amounts of branched chain α-keto acids alone or in combination with other antiglutamate agents such as L-methionine S-sulfoximine, L-ethionine S-sulfoximine, and glufosinate. In particular, the present invention relates to the treatment or prevention of diseases or conditions which are characterized by increased levels of brain neuronal glutamate.

The present invention is directed to cyclopropyl piperidine compounds that inhibit the glycine transporter GlyT1 and which are useful in the treatment of neurological and psychiatric disorders associated with glycinergic or glutamatergic neuro-transmission dysfunction and diseases in which the glycine transporter GlyT1 is involved.

The invention provides a preparation method of neural stem cells and glutamatergic neurons in cerebral cortex, and relates to an iPSC complete neural induction culture medium. The iPSC complete neuralinduction culture medium comprises the following components: a cell basic culture medium, a cell culture additive, neural development factors and an inhibitor. The invention provides the iPSC complete neural induction culture medium, an iPSC nerve cell culture medium and a culture method. The culture medium includes a serum-free basic medium, a cell additive, neural development factors and an inhibitor. The use of the serum-free basic medium can avoid the introduction of exogenous substances and reduce the risk of pollution. Meanwhile, a variety of nutrients, such as the cell additive and theneural development factors, can enable iPSC cells to be stimulated by signals so that iPSC cells can be activated to promote differentiation. The cell culture method provided by the invention is simple, efficient, low in cost, and can induce high-quality neuron cells in a short period.

A self-renewing restricted stem cell population has been identified in developing (embryonic day 13.5) spinal cords that can differentiate into multiple neuronal phenotypes, but cannot differentiate into glial phenotypes. This neuronal-restricted precursor (NRP) expresses highly polysialated or embryonic neural cell adhesion molecule (E-NCAM) and is morphologically distinct from neuroepithelial stem cells (NEP cells) and spinal glial progenitors derived from embryonic day 10.5 spinal cord. NRP cells self renew over multiple passages in the presence of fibroblast growth factor (FGF) and neurotrophin 3 (NT-3) and express a characteristic subset of neuronal epitopes. When cultured in the presence of RA and the absence of FGF, NRP cells differentiate into GABAergic, glutaminergic, and cholinergic immunoreactive neurons. NRP cells can also be generated from multipotent NEP cells cultured from embryonic day 10.5 neural tubes. Clonal analysis shows that E-NCAM immunoreactive NRP cells arise from an NEP progenitor cell that generates other restricted CNS precursors. The NEP-derived E-NCAM immunoreactive cells undergo self renewal in defined medium and differentiate into multiple neuronal phenotypes in mass and clonal culture. Thus, a direct lineal relationship exists between multipotential NEP cells and more restricted neuronal precursor cells present in vivo at embryonic day 13.5 in the spinal cord. Methods for treating neurological diseases are also disclosed.

A compound with general formula Ifor treatment of various diseases of the central nervous system, in treatment of neuropsychiatric disorders related to imbalance of glutamatergic neurotransmitter system, ischemic damage of CNS, neurodegenerative changes and disorders of CNS, affective disorders, depression, PTSD and other diseases related to stress, anxiety, schizophrenia and psychotic disorders, pain, addictions, multiple sclerosis, epilepsy and gliomas.

This invention provides a method of enhancing NMDAR-mediated neurotransmission in a disease associated with NMDAR antibody production, said method comprising administering an NMDAR agonist, an alanine-serine-cysteine transporter inhibitor, a D-amino acid oxidase inhibitor, a glycine transport inhibitor or a combination thereof to said subject. This invention also provides a method of mitigating the severity of, mitigating the pathogenesis of, lowering the incidence of or treating a disease associated with NMDAR antibody production, said method comprising administering an agent, which is an NMDAR agonist, an alanine-serine-cysteine transporter inhibitor, a D-amino acid oxidase inhibitor, a glycine transport inhibitor or a combination thereof to said subject.

The present invention relates to Chemistry, Pharmaceutical and in particular to the preparation of formulations from derivatives of phenolic or polyphenolic compounds and from derivatives of phenolic or polyphenolic compounds combined with tricyclic systems of the benzodiazepine type fused to derivatives of 1,4-dihydropyridines with action on the Central Nervous and Vascular Systems.These pharmaceutical compositions exhibit GABAergic, antiglutamatergic, calcium channel modulating, mitoprotective, anti-oxidant, anti-inflammatory, and antiapoptotic action, usable in the treatment of cardiovascular, cerebrovascular, neurodegenerative, neuropsychiatric and neurological diseases.

The present invention relates to iPSC produced from fibroblast obtained from a subject affected by a neurodevelopmental disorder entailing intellectual disability (ID) and / or a disorder belonging to the Autism Spectrum Disorder (ASD) and / or Schizophrenia (SZ) and uses thereof. The present invention also relates to a cortical neural progenitor cell or a terminally differentiated cortical glutamatergic or gabaergic neuronal cell or a neural crest stem cell line, a mesenchymal stem cell line produced from the iPSC or iPSC line. The invention also relates to method for identifying a compound for the treatment and / or prevention of a neurodevelopmental disorder entailing intellectual disability (ID) and / or a disorder belonging to the Autism Spectrum Disorder (ASD) and / or Schizophrenia (SZ) and to a LSD1 inhibitor or a HDAC2 inhibitor for use in the treatment of such disorders.

Disclosed in the present invention is a compound of Formula (I), a geometric or optical isomer, a pharmaceutically acceptable salt, a solvate or a polymorph thereof. Also disclosed in the present invention is a composition comprising the compound of Formula (I), the geometric or optical isomer, the pharmaceutically acceptable salt, the solvate or the polymorph thereof. Also disclosed in the present invention is a use of the compound of Formula (I), the geometric or optical isomer, the pharmaceutically acceptable salt, the solvate or the polymorph thereof in the treatment of a disease or disorder such as a hypoglutamatergic condition, a neurodegenerative disease or respiratory depression, particularly in the treatment of a disease or disorder associated with AMPA receptor.

The present invention relates to novel spiro-quinazolinone derivatives as positive allosteric modulators for modulating metabotropic glutamate receptor subtype 4 (mGluR4) and / or altering glutamate level or glutamatergic signalling.

The invention discloses an RNA (Ribonucleic Acid) composition for inducing neuronal differentiation. The RNA composition comprises a modified mRNA (Messenger Ribonucleic Acid) and a MicroRNA composition, the invention also provides a method for inducing differentiation of cortical glutamic acid energetic neurons by using the RNA composition, and pluripotent stem cells can be induced to be differentiated into neurons within seven days through transient overexpression of the mRNA and MicroRNA composition; the invention also provides an application of the RNA composition, and the RNA composition is used for inducing cortical glutamic acid neurons to differentiate. The transfection process and the mRNA delivery system are optimized, so that the translation efficiency of transfected mRNA and the expression quantity of mRNA in cells are remarkably improved. The method is suitable for inducing the differentiation of the cortical glutamic acid neurons, and the differentiated cortical glutamic acid neurons can be further applied to the construction of pathological models of human nerve-related diseases.

The present invention relates to novel substituted pyridine derivatives as positive allosteric modulators for modulating metabotropic glutamate receptor subtype 3 (mGluR3) and / or altering glutamate level or glutamatergic signalling.