41 results about "CREB" patented technology

The present invention provides methods of therapy of cognitive deficits associated with a central nervous system disorder or condition, methods of enhancing cognitive performance and methods for repeated stimulation of neuronal activity or a pattern of neuronal activity, such as that underlying a specific neuronal circuit(s). The methods comprise combining cognitive training protocols and a general administration of CREB pathway-enhancing agents.

The present invention provides a method for identifying an agent to be tested for an ability to treat a psychotic disorder in a patient in need of such treatment. The invention provides a method for screening candidate drugs for anti-psychotic drug activity, preferably atypical anti-psychotic activity, comprising contacting cells or tissues with a candidate drug, determining levels of phosphorylation of the intracellular signaling proteins, DARPP-32, ERK1, ERK2 and CREB, in said cells or tissues and determining the pattern of the levels of phosphorylation of the proteins. The pattern of the levels of phosphorylation of DARPP-32, ERK1, ERK2 and CREB is, in certain embodiments, compared with the pattern of the levels of phosphorylation of DARPP-32, ERK1, ERK2 and CREB in the presence of an atypical anti-psychotic drug.

In accordance with the present invention, it has been discovered that glucose and incretin hormones promote pancreatic islet cell survival via the calcium and cAMP dependent induction, respectively, of the transcription factor CREB. Specifically, a signaling module has been identified which mediates cooperative effects of calcium and cAMP on islet cell gene expression by stimulating the dephosphorylation and nuclear entry of TORC2, a cytoplasmic CREB coactivator. The module comprises a cAMP regulated snf1-like kinase called SIK2 and the calcium regulated phosphatase calcineurin, both of which associate with TORC2 in the cytoplasm. TORC2 is repressed under basal conditions through a phosphorylation dependent interaction with 14-3-3 proteins. cAMP and calcium signals stimulate CREB target gene expression via complementary effects on TORC2 dephosphorylation; cAMP disrupts TORC2-associated activity of SIK2 or related family members, whereas calcium induces TORC2 dephosphorylation via calcineurin. These findings provide a novel mechanism by which CREB activates cellular gene expression, depending on nutrient and energy status, and facilitate development of assays to identify compounds which modulate the role of TORCs. In accordance with the present invention, it has been discovered that fasting and energy-sensing pathways regulate the gluconeogenic program in liver by modulating the nuclear entry of a transcriptional coactivator called Transducer of Regulated CREB Activity 2 (TORC2). Hepatic TORC2 over-expression induces fasting hyperglycemia, whereas knockdown of TORC2 leads to fasting hypoglycemia and silencing of the gluconeogenic program. Since a majority of individuals with Type II diabetes exhibit fasting hyperglycemia due to elevated hepatic gluconeogenesis, compounds that enhance TORC2 phosphorylation will find use as therapeutic agents in this setting.

The invention relates to applications of Artepillin C and an analogue thereof in preparing drugs used for preventing metabolic diseases. The extremely excellent effect of Artepillin C or the analogue in preventing metabolic diseases is disclosed for the first time, and multifunctional drugs used for conditioning taking CREB/CRTC2 and SREBP as target spots are provided.

The present invention relates to a broad range of methods that utilize a transducer of regulated CREB (TORC)-related polynucleotide, polypeptide, or TORC-specific antibody. In addition the invention relates to TORC-related polynucleotide, polypeptide, or TORC-specific antibody compositions, including variants of TORC wild-type sequences. Exemplary methods include a method of stimulating a TORC related process in a cell as well as a method of inhibiting a TORC-related process in a cell, and a method of inhibiting TORC-related processes in a cell. The invention additionally discloses therapeutic methods of substantially inhibiting the development of, treating, or ameliorating a disease or pathological condition in a subject related to an abnormal level of a TORC-activated process in a cell that includes administering one or more therapeutically effective doses to the subject of either a substance that modulates accumulation of a TORC polypeptide in a subcellular region of the cell, or of a substance that inhibits expression of a TORC polypeptide in the cell. In an additional aspect a method of identifying an agent that modulates the activity of a TORC-related process in a cell is disclosed. In still a further aspect the invention relates to a method of detecting the presence or quantifying the amount of a TORC polypeptide in a sample. In a further aspect, a method is disclosed of determining whether the amount of a TORC polypeptide in a sample differs from the amount of the TORC polypeptide in a reference. An additional aspect relates to a method of contributing to the diagnosis or prognosis of, or to developing a therapeutic strategy for, a disease or pathology in a first subject, wherein the subcellular localization of a TORC polypeptide in the pathology is known to differ from the subcellular localization of the TORC polypeptide in a nonpathological state.

The invention discloses a detection method for evaluating the safety of cell growth factor to promote tumor growth, which comprises the following steps: firstly, using a CFSE marker flow cytometry and a [<3>H] incorporation method to measure the speeds of cell division and cell growth respectively; secondly, measuring CREB passageway related genes and protein expression level, and measuring the phosphorylation level of a CREB protein, and the combination of CREB, CREM, ICER, CBP, P300 and a growth regulatory gene promoter; and finally, evaluating the clone forming number and the tumor volume. The method applies the molecular biology and the cell biological technology combining with in vitro and in vivo test results to evaluate the safety of the cell growth factor to promote the tumor growth. The method can also be used for evaluating the safety of other genetic engineering drugs.

Methods are provided for modulating CREB by administering a CREB-specific modulator. Also provided are methods for treating cardiovascular and metabolic disorders in a subject or delaying or preventing risk factors thereof through the modulation of CREB. The present invention is also directed to methods of decreasing lipid levels in a subject or for preventing or delaying the onset of a rise in lipid levels in a subject, comprising administering to said subject a CREB-specific inhibitor.

The ospF gene of Shigella flexneri encodes a phosphatase, which is a member of a new class of phosphatases. The OspF phosphatase inhibits the activity of several proteins either by direct protein modification or transcription downregulation. These proteins include MAP kinase, IL-8, CCL20, IL-12, AP1, CREB, RPA p32, and BCL2 related proteins. Methods for treating diseases using OspF phosphatase, methods for identifying agents that modulate OspF phosphatase's activity, methods for identifying agents that mimic OspF phosphatase's activity, and immunogenic compositions comprising OspF phosphatase are provided. A strain of Shigella flexneri containing an inactivated ospF gene is also provided.

In accordance with the present invention, it has been discovered that CREB regulates hepatic gluconeogenesis via the co-activator, PGC-1. PGC-1 potentiated glucocorticoid induction of the gene for PEPCK, the rate limiting enzyme in gluconeogenesis, via the glucocorticoid response unit in the promoter, indicating that activation of PGC-1 by CREB in liver contributes to the pathogenesis of diabetes mellitus. In accordance with the above discoveries, the present invention provides a method of identifying a compound that modulates gluconeogenesis. The invention method comprises contacting CREB and a nucleic acid comprising a PGC-1 promoter with a test compound, and determining if the test compound modulates binding between CREB and the PGC-1 promoter.

The invention discloses a medicine composition for treating depression, which is prepared from panaxoside Rg1, Rb1 and glycyrrhizic acid (glycyrrhetinic acid), and a preparation method of the medicine composition. Proven by a test, the medicine composition can obviously reduce the tail suspension and immobility time during forced swimming, can rapidly arouse the CAMP-PKA access of a hippocampus and improves the expressions of CREB and BDNF. Accordingly, the medicine composition can be used for treating depression acted on the body.

According to the experimental results of the invention, UCA1 has a negative regulatory effect on melanogenesis of melanocytes, and the expression level of melanogenesis-related genes is decreased after overexpression of UCA1 in melanocytes, and is obviously enhanced after UCA1 is knocked out, and UCA1 negatively regulates melanogenesis mainly through a cAMP/PKA/CREB pathway. The results of this study suggest that UCA1 is a potential therapeutic target for regulating melanogenesis in melanocytes, and the development of drugs or treatments that regulate the expression level of UCA1 is expected to bring new hope to the treatment of hyperpigmentation dermatoses.

The present method relates to quantification of prognostic and predictive biomarkers of the PDK/AKT/mTOR pathway, such as GSK3β, S6, CREB, PTEN, AKT and mTOR, using AQUA® analysis to estimate both patient risk and benefit of treatment to patients diagnosed with glioblastoma. Unlike traditional IHC, the AQUA® system is objective and produces quantitative in situ protein expression data on a continuous scale. Taking advantage of the power of the AQUA system, the present method provides a highly robust and standardized diagnostic assays that can be used in the clinical setting to provide physicians with reliable prognostic and predictive information. Glioblastoma multiform (GBM) remains one of the most aggressive human cancers, and biomarkers that provide prognostic and predictive information would be extremely valuable to both the physician and the patient. A patient's risk may be determined using the prognostic biomarkers of the present method. Such a prognostic determination will allow physicians to identify patients with a relatively ‘good’ or a relatively ‘poor’ prognosis. The benefit of treating specific patients with a specific therapy, may be determined usin̂ the predictive markers of the present method. Treatment with the AGC-family kinase inhibitor enzastaurin, for example, identifies patients that will likely benefit from treatment or not.

The invention belongs to the field of pharmaceutical chemistry, and in particular relates to novel applications of pegylated curcumin derivative, especially the applications of the pegylated curcumin derivative in preparing medicines for preventing or treating fatty liver diseases and atherosclerosis. The experiment proves that the pegylated curcumin derivative can reduce the level of triglyceride in the blood, activate the phosphorylation of cyclic-AMP response element binding protein (CREB), negatively regulate nuclear transcription receptor PPAR gamma closely related to lipid metabolism, reduce the CD36 expression of the lever tissue caused by high fat diet, reduce the intake of fatty acid of the liver, reduce the lipid formation of the liver, and improve the fatty degeneration of the liver. The pegylated curcumin derivative further can improve the level of high density lipoprotein cholesterol, promote the reverse cholesterol transport, reduce the CD36 expression of macrophages, reduce the intake of oxidized low density lipoprotein, alleviate the bubblization of the macrophages, and reduce the deposition of lipid on the endangium and the formation of artery atherosclerotic plaque.

The invention provides a method of extracting whole coffee fruit, an extract obtained from the method, and method of ameliorating age-related neurodegenerative diseases using said extract. The whole coffee fruit extract may be extracted by water, methanol, ethanol, or acetone and may comprise chlorogenic acid (CA) and procyanidine. The expression levels of p-CREB, BDNF, p-eIF2α, BACE-1, Aβ, NLRP3, caspase-1, IL-1β and COX-2 which may relate to age-related neurodegenerative diseases can be modulated.

The invention provides a traditional Chinese medicine composition for promoting regeneration of hippocampal neurons. The composition is prepared from the following components in parts by weight: 5-20parts of acanthopanax roots, 5-20 parts of medicinal Indian mulberry roots, 5-20 parts of turmeric root tuber, 1-15 parts of polygala roots, 5-20 parts of platycladi seeds, 3-15 parts of Chinese magnoliavine fruits, 5-20 parts of nutgrass galingale rhizome, 1-10 parts of lotus plumules, 3-15 parts of prepared pinellia tubers and 1-10 parts of pseudo-ginseng. The traditional Chinese medicine composition can be used for promoting regeneration of hippocampal neurons and regulating 5-HT1AR mediated CAMP-CREB-BDNF channel so as to achieve the effect of treating depression.

A method of screening for a therapeutic and/or preventive drug for cartilaginous hyperplasia and a therapeutic and/or preventive drug for cartilaginous hyperplasia are provided.

The following are provided: a method of screening for a therapeutic and/or preventive drug for cartilaginous hyperplasia, comprising a step of culturing chondroprogenitor cells under conditions in which the cells are brought into contact with a test substance and conditions in which the cells are not brought into contact with the test substance and a step of determining the SOX9 promoter activity, cAMP level, or degree of phosphorylation of CREB in the cells or the extracellular matrix volume in a culture; and a therapeutic and/or preventive drug for cartilaginous hyperplasia, comprising as an active ingredient an adenylate cyclase inhibitor.

The invention provides a method for efficiently inducing human cells to be reprogrammed into neuronal cells. The concentration of cAMP is improved or the expression of PKA and CREB is up-regulated or the expression of AMPK, ALK2, ALK3, P38 and JNK is inhibited through a single small molecule compound or gene knockout or gene overexpression. The induced small molecule compound is single and safe, short in induction time, high in induction efficiency, clear in induction action site and gene and clear in molecular regulation mechanism, can be applied to clinical treatment of human neurodegenerative diseases, and provides a safer and more efficient treatment means for treatment of the neurodegenerative diseases. As neurons do not have division and proliferation capacities, fibroblasts and astrocytes with division and proliferation capacities can be induced in vivo and in vitro by utilizing the method; and a large number of induced neurons can be continuously obtained in vivo and in vitro.

It is the first time for the invention to disclose that a rhodanine derivative can activate STAT3, CREB and PPARs signal paths, significantly increase expression of UCP1, enhance expression of mitochondrial oxidative phosphorylation genes, effectively increase thermogenesis, and can be used for treating the metabolic diseases. Accordingly, the invention relates to application of the rhodanine derivative to treatment of the metabolic diseases. The invention further relates to a pharmaceutical composition containing the rhodanine derivative as an active ingredient, and the pharmaceutical composition is used for treatment of the metabolic diseases.

The invention belongs to the technical field of the biology, and discloses an analytical method of CREB in Ang-2 regulating VEGFR2 expression. By combining the gene knockout, signal channel inhibitionand like technical measures, the important effect of the CREB in the Ang-2 regulating VEGFR2 expression process is verified, and the determined protein is expressed through a protein expression unit;partial protein expression unit is optimized by adopting a to-be-screened compound; the protein expression quantity is compared with the protein expression quantity in a set reference system, a protein expression result is analyzed to obtain related conclusion for detecting gene toxicity activity. At least partial system is incubated by using the to-be-screened compound, and the protein expression in the system is compared with the protein expression in the reference system, thereby detecting the (front-) gene toxicity activity. The theoretical evidence is provided for the analysis of the CREB in the Ang-2 regulating VEGFR2 expression.

The present disclosure is directed to solid and salt forms of inhibitors of the CBP/p300 family of bromodomains made up of salts and crystalline forms of Formula (I). The compounds can be useful in the treatment of disease or disorders associated with the inhibition of the CBP/p300 family of bromodomains. For instance, the disclosure is concerned with compounds and compositions for inhibition of the CBP/p300 family of bromodomains, methods of treating diseases or disorders associated with the inhibition of CBP/p300 family of bromodomains (e.g., certain forms of cancer), and methods of synthesis of these compounds.