Abstract: The present invention relates to the use of p11 as a drug target as well as a tool for the diagnosis, treatment and development of p11/5-HT receptor related disorders. The invention further relates to p11 knock-out animals as well as p11 transgenic animals and their use as models for the development of novel psychotherapeutic agents, and to methods of diagnosis, prophylaxis and treatment of p11/5-HT receptor related disorders.

Abstract: The present invention provides methods and compositions for modulating levels of amyloid-? peptide (A?) exhibited by cells or tissues. The invention also provides pharmaceutical compositions and methods of screening for compounds that modulate A? levels. The invention also provides modulation of A? levels via selective modulation (e.g., inhibition) of ATP-dependent ?-secretase activity. The invention also provides methods of preventing, treating or ameliorating the symptoms of a disorder, including but not limited to an A?-related disorder, by administering a modulator of ?-secretase, including, but not limited to, a selective inhibitor of ATP-dependent ?-secretase activity or an agent that decreases the formation of active (or optimally active) ?-secretase. The invention also provides the use of inhibitors of ATP-dependent ?-secretase activity to prevent, treat or ameliorate the symptoms of Alzheimer's disease.

Abstract: Methods and compositions are provided for translational profiling and molecular phenotyping of specific tissues, cells and cell subtypes of interest. The methods provided herein facilitate the analysis of gene expression in the selected subset present within a heterogeneous sample.

Abstract: The present invention provides methods and compositions for modulating levels of amyloid-? peptide (A?) exhibited by cells or tissues. The invention also provides pharmaceutical compositions and methods of screening for compounds that modulate A? levels. The invention also provides modulation of A? levels via selective modulation (e.g., inhibition) of ATP-dependent ?-secretase activity. The invention also provides methods of preventing, treating or ameliorating the symptoms of a disorder, including but not limited to an A?-related disorder, by administering a modulator of ?-secretase, including, but not limited to, a selective inhibitor of ATP-dependent ?-secretase activity or an agent that decreases the formation of active (or optimally active) ?-secretase. The invention also provides the use of inhibitors of ATP-dependent ?-secretase activity to prevent, treat or ameliorate the symptoms of Alzheimer's disease.

Abstract: The present invention relates to the use of p11 as a drug target as well as a tool for the diagnosis, treatment and development of p11/5-HT receptor related disorders. The invention further relates to p11 knock-out animals as well as p11 transgenic animals and their use as models for the development of novel psychotherapeutic agents, and to methods of diagnosis, prophylaxis and treatment of p11/5-HT receptor related disorders.

Abstract: The invention provides methods for treating A? peptide related disorders such as Alzheimer's disease comprising administering a therapeutically effective amount of a CK1 modulator to a patient in need thereof.

Abstract: Treatment of neurodegenerative diseases is achieved using small molecule purine scaffold compounds that inhibit Hsp90 and that possess the ability to cross the blood-brain barrier or are other wise delivered to the brain.

Abstract: Disclosed herein are compositions and methods relating to peptides. The peptides can inhibit amyloid beta (A?) generation and reduce GSK-3 activities. Further provided are compositions and methods for treating or preventing, for example, Alzheimer's disease, cancer, and diabetes.

Abstract: 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.

Abstract: Methods are provided for screening agents for activity as modulators of calcium signaling in brain tissue.

Abstract: The present invention provides methods and compositions for modulating the activity of phosphodiesterase 1B (PDE1B) in intracellular signaling pathways, including but not limited to, dopamine D1 intracellular signaling pathways. The invention also provides methods and compositions for modulating the activities of intracellular signaling molecules, including, but not limited to, DARPP-32 and GluR1 AMPA receptor, via modulation of PDE1B. The invention also provides pharmaceutical compositions and methods of screening for compounds that modulate PDE1B activity. The invention also provides methods of treating or ameliorating the symptoms of a disorder, including but not limited to a PDE1B-related disorder or a dopamine D1 receptor intracellular signaling pathway disorder, by administering a modulator of PDE1B, preferably, but not limited to, an inhibitor of PDE1B or an agent that decreases the production of PDE1B.

Abstract: The present invention provides methods and compositions for modulating the phosphorylation of DARPP-32 in a serotonergic receptor intracellular signaling pathway. The invention provides methods and compositions for modulating the activities of DARPP-32, casein kinase 1 (CK1), cyclin-dependent kinase 5 (Cdk5), AMPA receptors, protein phosphatase-1 (PP-1), protein phosphatase 2C (PP2C), protein phosphatase 2B (PP2B) and/or protein phosphatase 2A (PP2A) in cells or tissues. The invention provides methods of treating serotonergic intracellular signaling pathway disorders, e.g., depression. The invention provides methods of treating dopamine-related disorders. The invention provides methods of identifying agents that modulate the activities of serotonergic receptor intracellular signaling molecules, DARPP-32, casein kinase 1, cyclin-dependent kinase 5, AMPA receptors, protein phosphatase-1, protein phosphatase 2C, protein phosphatase 2B and/or protein phosphatase 2A, for use in such treatments.

Abstract: Compounds and compositions including 6-bromo-indirubin, 5-amino-indirubin and N-methyl-indirubins and related indirubin derivatives are provided that are useful as selective modulators of glycogen synthase kinase-3, cyclin-dependent protein kinases or aryl hydrocarbon receptors. Methods of inhibiting or modulating cell growth or cell cycling are provided using the compounds of the invention. In other aspects, compounds and methods for the treatment of protozoan-mediated diseases, Alzheimer's disease and diabetes are provided.

Abstract: The present invention provides methods and compositions for modulating the activities of metabotropic glutamate receptor intracellular signaling molecules. The present invention provides methods and compositions for modulating the activities of casein kinase I and/or cyclin-dependent kinase 5 in cells or tissues. The present invention provides methods of modulating the function of calcium channels in cells or tissues. The present invention provides methods of treating calcium channel dysfunction. The present invention provides methods of identifying agents that modulate the activities of the metabotropic glutamate receptor intracellular signaling molecules casein kinase I and/or cyclin-dependent kinase 5 for use in such treatments.

Abstract: The present invention provides methods and compositions for modulating the activities of metabotropic glutamate receptor intracellular signaling molecules. The present invention provides methods and compositions for modulating the activities of casein kinase I and/or cyclin-dependent kinase 5 in cells or tissues. The present invention provides methods of modulating the function of calcium channels in cells or tissues. The present invention provides methods of treating calcium channel dysfunction. The present invention provides methods of identifying agents that modulate the activities of the metabotropic glutamate receptor intracellular signaling molecules casein kinase I and/or cyclin-dependent kinase 5 for use in such treatments.

Abstract: The present invention discloses that DARPP-32 is substrate for the cyclin dependent kinase Cdk5. The phosphorylation takes place at a specific threonine residue of DARPP-32 (Threonine 75). The Cdk5 catalyzed phosphorylation of DARPP-32 converts this protein into an inhibitor of the cAMP dependent protein kinase (PKA) and furthermore prevents it from being converted to an inhibitor of protein phosphatase 1 (PP1). Methods of identifying agents that modulate the phosphorylation of DARPP-32 by Cdk5 are disclosed. Methods of treating dopamine dysfunction in animal subjects are also provided.

Abstract: Methods are provided for screening agents for activity as modulators of calcium signaling in brain tissue.

Abstract: The present invention provides methods and compositions for modulating levels of amyloid-&bgr; peptide (A&bgr;) exhibited by cells or tissues. The invention also provides pharmaceutical compositions and methods of screening for compounds that modulate A&bgr; levels. The invention also provides modulation of A&bgr; levels via selective modulation (e.g., inhibition) of ATP-dependent &ggr;-secretase activity. The invention also provides methods of preventing, treating or ameliorating the symptoms of a disorder, including but not limited to an A&bgr;-related disorder, by administering a modulator of &ggr;-secretase, including, but not limited to, a selective inhibitor of ATP-dependent &ggr;-secretase activity or an agent that decreases the formation of active (or optimally active) &ggr;-secretase. The invention also provides the use of inhibitors of ATP-dependent &ggr;-secretase activity to prevent, treat or ameliorate the symptoms of Alzheimer's disease.

Abstract: The present invention provides methods and compositions for modulating the activity of phosphodiesterase 1B (PDE1B) in intracellular signaling pathways, including but not limited to, dopamine D1 intracellular signaling pathways. The invention also provides methods and compositions for modulating the activities of intracellular signaling molecules, including, but not limited to, DARPP-32 and GluR1 AMPA receptor, via modulation of PDE1B. The invention also provides pharmaceutical compositions and methods of screening for compounds that modulate PDE1B activity. The invention also provides methods of treating or ameliorating the symptoms of a disorder, including but not limited to a PDE1B-related disorder or a dopamine D1 receptor intracellular signaling pathway disorder, by administering a modulator of PDE1B, preferably, but not limited to, an inhibitor of PDE1B or an agent that decreases the production of PDE1B.

Abstract: The present invention provides methods and compositions for modulating the phosphorylation of DARPP-32 in a serotonergic receptor intracellular signaling pathway. The invention provides methods and compositions for modulating the activities of DARPP-32, casein kinase 1 (CK1), cyclin-dependent kinase 5 (Cdk5), AMPA receptors, protein phosphatase-1 (PP-1), protein phosphatase 2C (PP2C), protein phosphatase 2B (PP2B) and/or protein phosphatase 2A (PP2A) in cells or tissues. The invention provides methods of treating serotonergic intracellular signaling pathway disorders, e.g., depression. The invention provides methods of treating dopamine-related disorders. The invention provides methods of identifying agents that modulate the activities of serotonergic receptor intracellular signaling molecules, DARPP-32, casein kinase 1, cyclin-dependent kinase 5, AMPA receptors, protein phosphatase-1, protein phosphatase 2C, protein phosphatase 2B and/or protein phosphatase 2A, for use in such treatments.