326results about "Receptors for neuromediators" patented technology

Tandem pore domain weak inward rectifying K+ (TWIK) channel nucleic acids and proteins that have been isolated from Drosophila melanogaster and Leptinotarsa are described. The TWIK channel nucleic acids and proteins can be used to genetically modify metazoan invertebrate organisms, such as insects, coelomates, and pseudocoelomates, or cultured cells, resulting in TWIK channel expression or mis-expression. The genetically modified organisms or cells can be used in screening assays to identify candidate compounds which are potential pesticidal agents or therapeutics that interact with TWIK channel proteins. They can also be used in methods for studying TWIK channel activity and identifying other genes that modulate the function of, or interact with, the TWIK channel gene.

The disclosed invention relates to selective VPAC1 antagonists, related formulations, dosages and methods of use. The selective VPAC1 antagonists of the invention comprise a vasoactive intestinal peptide component and a growth hormone releasing hormone component capable of selectively binding to and antagonizing the VPAC1 receptor at significantly lower concentrations than those concentrations at which it binds to and antagonizes the VPAC2 receptor.

The present invention is directed to methods for identification of compounds that affect wakefulness, attention deficit hyperactivity disorder, chronic fatigue syndrome and mood disorders (e.g., depression) through interaction with the hypocretin receptor system. The present invention is also directed to detection of abnormal levels of hypocretin in a subject, as well as detection of an abnormal immune response against hypocretin (orexins) and/or their receptors, where detection of abnormal hypocretin levels or detection of an abnormal immune response is indicative of a sleep disorder, particularly of narcolepsy. The present invention is also directed to a methods relating to the detection of a mutation or polymorphism in the gene encoding the hypocretin receptors, the detection of antibodies disrupting the function of gene encoding hypocretin receptors and hypocretin polypeptides, and the use of hypocretin biological markers in predicting treatment response using compounds interacting with the hypocretin receptor system.

The present invention provides Orphanin FQ receptor nucleic acids and polypeptides and uses thereof. In particular, the present invention provides nucleic acid sequences of differentially expressed splice variants of the Orphanin FQ receptor. The present invention also provides methods of using the Orphanin FQ receptor nucleic acid sequences and ligands for the identification of pharmaceutical agents, the generation of animal models of Orphanin FQ receptor-mediated disease states, and for formulating biological activities. The present invention further provides improved methods of screening potential therapeutics useful in the treatment of a variety of disease states mediated by Orphanin FQ signaling, as well as therapeutics identified using the screening methods.

The application provides data from a clinical trial of a PSD-95 inhibitor in subjects undergoing endovascular repair of an aneurysm in or otherwise affecting the CNS. The subjects were stratified by whether the aneurysm ruptured before performing the endovascular surgery. Rupture is associated with higher mortality or increased debilitation if a subject survives. The trial provided evidence of significant benefit in subjects with and without aneurysm rupture before endovascular was surgery performed. Surprisingly, the subjects benefiting most from treatment as judged both by pathology and neurocognitive outcome were those in which the aneurysm had ruptured causing a subarachnoid hemorrhage. These data constitute evidence that a PSD-95 inhibitor is beneficial not only in ischemic and hemorrhagic stroke but in forms of hemorrhage in or affecting the CNS, particularly, subarachnoid hemorrhage.

A method of crystallizing a molecule-of-interest is disclosed. The method comprises (a) contacting molecules of the molecule-of-interest with at least one type of heterologous molecular linker being capable of interlinking at least two molecules of said molecule-of-interest to thereby form a crystallizable molecular complex of defined geometry; and (b) subjecting said crystallizable molecular complex to crystallization-inducing conditions, thereby generating the crystal containing said molecule-of-interest.

Provided herein are compositions and methods for gene and etiology-nonspecific and circuit-specific treatment of diseases, utilizing vectors for delivery of light-sensitive proteins to diseased and normal cells and tissues of interest.

A screening method for identifying compounds that are effective insect control agents includes providing cells expressing an octopamine receptor, adding the compounds to the cells, and measuring the effects of the compounds and compositions. The effects of the compounds may be determined by measuring the binding affinity of the compounds to the octopamine receptor or measuring the change in intracellular cAMP or Ca²⁺ levels.

This invention relates to polymorphisms in the human mGluR8, in particular to the discovery of 10 single nucleotide polymorphisms in the mGluR8 gene. The invention also relates to methods and materials for analyzing allelic variation in the mGluR8 gene, and to the use of mGluR8 polymorphism in the diagnosis and treatment of mGluR8 and/or mGluR8-mediated diseases, such as Parkinson s disease etc. The herein disclosed probes containing at least one of the herein disclosed SNPs can be used to identify nucleic acid samples containing mGluR8 SNPs or as primers or for expressing variant proteins. Methods of analyzing the polymorphic forms occupying the polymorphic sites are also disclosed.

The present invention provides an isolated nucleic acid molecule comprising, or consisting of, the nucleic acid sequence of SEQ ID NO:1 or a nucleic acid sequence of at least 400 bp having at least 80% identity to said sequence of SEQ ID NO:1, wherein said isolated nucleic acid molecule specifically leads to the expression in Muller cells of a gene when operatively linked to a nucleic acid sequence coding for said gene.

Inhibitors of Nogo Receptor (NgR)-p75 binding are used to reduce NgR-p75 binding mediated axon growth inhibition. Mixtures of NgR and p75 are used in pharmaceutical screens to characterize agents as inhibiting binding of NgR to p75 and promoting axon regeneration.

Y receptor agonists other than PYY 3-36, which are selective for the Y2 receptor over the Y1 and Y4 receptors, and their use in the treatment of conditions responsive to activation of Y2 receptors, are disclosed. Broadly, a Y2-selective agonist is one which (a) is a PP-fold peptide or PP-fold peptide mimic selected from PYY, NPY, PYY mimics and NPY mimics which have a C-terminal Y2 receptor-recognition amino acid sequence and have various modifications relative to the natural peptides or (b) a PP-fold peptide or PP-fold peptide mimic selected from PP and PP-mimics which have a C-terminal Y2 receptor-recognition amino acid sequence and which have various modifications relative to the natural peptide or (c) comprise a C-terminal Y2 receptor-recognition amino acid sequence fused at its N-terminus to an amphiphilic amino acid sequence domain comprising at least one alpha helical turn adjacent the N-terminus of the said Y2 receptor-recognition sequence, said turn being constrained in a helical configuration by a covalent intramolecular link, and (ii), in the case where the agonist has an N-terminal structure analogous to NPY or PYY, having one or more of the modifications listed in (a) above and, in the case where the agonist has an N-terminal structure analogous to PP, having one or more of the modifications listed in (b) above.

The present invention relates e.g., to QM-7 or QT-6 cells comprising a heterologous mutant nicotinic α7 acetylcholine receptor and/or a nucleic acid encoding it, or a fragment or variant thereof. In a preferred embodiment, the mutant nicotinic α7 acetylcholine receptor subunit has a mutation in the M2 domain. QM-7 and QT-6 cells of the invention are useful for, e.g., assays such as high throughput assays that measure the influx of cations, such as Ca⁺⁺ ions, into a cell. Such assays can be used, e.g., to identify agents that modulate the expression and/or activity of a mutant cell-surface-expressed channel receptor (e.g., the nicotinic α7 receptor), and which thus modulate, e.g., among other functions, processes involved in the central nervous system, such as learning and memory.

Peptides having at least nine amino acid residues each including an amino acid sequence which corresponds to position p200-208 or p262-266 of the human acetylcholine receptor alpha -subunit, but differing therefrom by one or more amino acid substitutions, are disclosed. These peptides inhibit the proliferative response of human peripheral blood lymphocytes to the myasthenogenic peptides p195-212 and p259-271 and are suitable for treatment of subjects afflicted with myasthenia gravis.

The inventors have succeeded in discovering that the p75 neurotrophin receptor (p75NTR) is directly involved in the degradation of cAMP via interaction of its intracellular domain with phosphodiesterase 4A4/5 (PDE4A4/5). Provided herein are methods and compositions for the treatment of conditions of PDE4A4/5 and p75NTR expression (such as pulmonary disease and nerve regeneration) by blocking the interaction of PDE4A4/5 and p75NTR, as well as methods for the screening of agents useful in such applications.

There is provided a series of novel neuropeptide Y-cytotoxic conjugates, compositions comprising the same, and methods relating to their therapeutic use for the treatment of disease or condition states associated with aberrant or undesirable proliferation of cells that express NPY-Y1 receptors.