Abstract: The present invention relates to cells and methods for detecting compounds that affect G protein coupled receptor mediated conditions. The invention also relates to methods for treating adverse drug reactions, autoimmune disorders, and pruritus.

Abstract: The present invention relates to cells and methods for detecting compounds that affect G protein coupled receptor mediated conditions. The invention also relates to methods for treating adverse drug reactions, autoimmune disorders, and pruritus.

Abstract: The disclosure provides methods for (i) treating multiple sclerosis in patient, (ii) treating a patient having symptoms of multiple sclerosis, (iii) preventing the onset of multiple sclerosis symptoms in patient having multiple sclerosis or predisposed to multiple sclerosis; (iv) promoting or enhancing immunomodulation and remyelination and/or myelin repair in a subject in need thereof; (v) a neuroinflammatory disorder; (vi) Amyotrophic Lateral Sclerosis; or (vii) a demyelinating disease or disorder or a hypomyelinating condition, each method comprising administering a therapeutically effective amount of a bryostatin compound to the patient.

Abstract: Described herein are methods for modulation of the activity of the carotid body that afford therapeutic benefit for sleep-related breathing disorders and related conditions.

Abstract: The present invention relates to cells and methods for detecting compounds that affect G protein coupled receptor mediated conditions. The invention also relates to methods for treating adverse drug reactions, autoimmune disorders, and pruritus.

Abstract: The present invention relates to the field of drug abuse. More specifically, the present invention provides methods and compositions for treating drug abuse by preventing GAPDH nitrosylation. In one specific embodiment, a method for preventing the stimulant and neurotoxic effects of cocaine comprises the step of administering a compound that prevents the nitrosylation of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) by nitric oxide (NO). In another embodiment, a method for preventing the stimulant and neurotoxic effects of cocaine comprises the step of administering a compound that prevents the binding of GAPDH to Siah.

Abstract: The present invention relates to the field of drug abuse. More specifically, the present invention provides methods and compositions for treating drug abuse by preventing GAPDH nitrosylation. In one specific embodiment, a method for preventing the stimulant and neurotoxic effects of cocaine comprises the step of administering a compound that prevents the nitrosylation of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) by nitric oxide (NO). In another embodiment, a method for preventing the stimulant and neurotoxic effects of cocaine comprises the step of administering a compound that prevents the binding of GAPDH to Siah.

Abstract: Described herein are methods for modulation of the activity of the carotid body that afford therapeutic benefit for sleep-related breathing disorders and related conditions.

Abstract: The atypical antipsychotic drugs (AAPDs) have markedly enhanced the treatment of schizophrenias but their use has been hindered by the major weight gain elicited by some AAPDs. We found that orexigenic AAPDs potently and selectively activate hypothalamic AMP kinase (AMPK), an action abolished in mice with deletion of histamine H1 receptors. These findings afford a means of developing better therapeutic agents and provide insight into the hypothalamic regulation of food intake.

Abstract: Anti-cancer drugs are identified by screening for agents and compounds which inhibit the binding of HSP90 and IP6K2. In vitro and in vivo assays can be used. Any phenomenon associated with the binding or inhibition can be monitored, including cell death, subcellular localization, catalytic activity of IP6K2, and IP7 formation.

Abstract: Anti-cancer drugs are identified by screening for agents and compounds which inhibit the binding of HSP90 and IP6K2. In vitro and in vivo assays can be used. Any phenomenon associated with the binding or inhibition can be monitored, including cell death, subcellular localization, catalytic activity of IP6K2, and IP7 formation.

Abstract: The atypical antipsychotic drugs (AAPDs) have markedly enhanced the treatment of schizophrenias but their use has been hindered by the major weight gain elicited by some AAPDs. We found that orexigenic AAPDs potently and selectively activate hypothalamic AMP kinase (AMPK), an action abolished in mice with deletion of histamine H1 receptors. These findings afford a means of developing better therapeutic agents and provide insight into the hypothalamic regulation of food intake.

Abstract: Cyclooxygenase (COX2) and inducible nitric oxide synthase (iNOS) are two major inflammatory mediators. Inducible NOS specifically binds to COX2 and S-nitrosylates it, enhancing COX2 catalytic activity. Selectively disrupting iNOS-COX2 binding prevents NO-mediated activation of COX2. The synergistic molecular interaction between two inflammatory systems permits assays for developing anti-inflammatory drugs.

Abstract: Cyclooxygenase (COX2) and inducible nitric oxide synthase (iNOS) are two major inflammatory mediators. Inducible NOS specifically binds to COX2 and S-nitrosylates it, enhancing COX2 catalytic activity. Selectively disrupting iNOS—COX2 binding prevents NO-mediated activation of COX2. The synergistic molecular interaction between two inflammatory systems permits assays for developing anti-inflammatory drugs.

Abstract: Many of the effects of nitric oxide are mediated by the direct modification of cysteine residues resulting in an adduct called a nitrosothiol. A method to detect proteins which contain nitrosothiols involves several steps. Nitrosylated cysteines are converted to tagged cysteines. Tagged proteins can then be detected, for example, by immunoblotting and/or can be purified by affinity chromatography. The method is applicable to the detection of S-nitrosylated proteins in cell lysates following in vitro S-nitrosylation, as well as to the detection of endogenous S-nitrosothiols in selected protein substrates.

Abstract: Many of the effects of nitric oxide are mediated by the direct modification of cysteine residues resulting in an adduct called a nitrosothiol. A method to detect proteins which contain nitrosothiols involves several steps. Nitrosylated cysteines are converted to tagged cysteines. Tagged proteins can then be detected, for example, by immunoblotting and/or can be purified by affinity chromatography. The method is applicable to the detection of S-nitrosylated proteins in cell lysates following in vitro S-nitrosylation, as well as to the detection of endogenous S-nitrosothiols in selected protein substrates.

Abstract: Disclosed are methods for preventing or treating a gastrointestinal (GI) disorder in a mammal such as a human patient. In one embodiment, the methods include administering to the mammal a therapeutically effective amount of a compound that modulates a nitric oxide (NO) signaling pathway, particularly in GI neurons. Methods of the invention are particularly useful for the treatment (including prophylactic treatment) of diabetic gastropathies and other GI disorders.

Abstract: This invention relates to the method of using neurotrophic cyclophilin inhibitor compounds having an affinity for cyclophilin-type immunophilins as inhibitors of the enzyme activity associated with immunophilin proteins, and particularly inhibitors of peptidyl-prolyl isomerase or rotamase enzyme activity.

Abstract: A protein complex containing 245 kDa and 35 kDa components, designated RAFT1 and RAFT2 (for Rapamycin And FKBP12 Target) interacts with FKBP12 in a rapamycin-dependent manner. This interaction has the pharmacological characteristics expected from the observed in vivo effects of rapamycin: it occurs at low nanomolar concentrations of rapamycin and is competed by excess FK506. Sequences (330 amino acids total) of tryptic peptides derived from the affinity purified 245 kDa RAFT1 reveals striking homologies to the predicted products of the yeast TOR genes, which were originally identified by mutations that confer rapamycin resistance in yeast. A RAFT1 cDNA was obtained and found to encode a 289 kDa protein (2550 amino acids) that is 43% and 39% identical to TOR2 and TOR1, respectively.

Abstract: A protein complex containing 245 kDa and 35 kDa components, designated RAFT1 and RAFT2 (for Rapamycin And FKBP12 Target) interacts with FKBP12 in a rapamycin-dependent manner. This interaction has the pharmacological characteristics expected from the observed in vivo effects of rapamycin: it occurs at low nanomolar concentrations of rapamycin and is competed by excess FK506. Sequences (330 amino acids total) of tryptic peptides derived from the affinity purified 245 kDa RAFT1 reveals striking homologies to the predicted products of the yeast TOR genes, which were originally identified by mutations that confer rapamycin resistance in yeast. A RAFT1 cDNA was obtained and found to encode a 289 kDa protein (2550 amino acids) that is 43% and 39% identical to TOR2 and TOR1, respectively.