Abstract: Compositions and methods are provided for biologically relevant in vitro screening of neural function, including determination of the effects of an agent on neural cells. The compositions of the invention useful in such screening methods include a neural co-culture system comprising human pluripotent stem cell (PSC)-derived neurons and human glial cells, which may be derived by culture methods allowing for rapid and robust development of highly mature neuronal activity, particularly spontaneous synchronous network bursts.

Abstract: Compositions and methods are provided for biologically relevant in vitro screening of neural function, including determination of the effects of an agent on neural cells. The compositions of the invention useful in such screening methods include a neural co-culture system comprising human pluripotent stem cell (PSC)-derived neurons and human glial cells, which may be derived by culture methods allowing for rapid and robust development of highly mature neuronal activity, particularly spontaneous synchronous network bursts.

Abstract: Methods, compositions and kits for producing functional neurons, astroctyes, oligodendrocytes and progenitor cells thereof are provided. These methods, compositions and kits find use in producing neurons, astrocytes, oligodendrocytes, and progenitor cells thereof for transplantation, for experimental evaluation, as a source of lineage- and cell-specific products, and the like, for example for use in treating human disorders of the CNS. Also provided are methods, compositions and kits for screening candidate agents for activity in converting cells into neuronal cells, astrocytes, oligodendrocytes, and progenitor cells thereof.

Abstract: Methods, compositions and kits for producing functional neurons, astroctyes, oligodendrocytes and progenitor cells thereof are provided. These methods, compositions and kits find use in producing neurons, astrocytes, oligodendrocytes, and progenitor cells thereof for transplantation, for experimental evaluation, as a source of lineage- and cell-specific products, and the like, for example for use in treating human disorders of the CNS. Also provided are methods, compositions and kits for screening candidate agents for activity in converting cells into neuronal cells, astrocytes, oligodendrocytes, and progenitor cells thereof.

Abstract: Methods, compositions and kits for producing functional neurons, astroctyes, oligodendrocytes and progenitor cells thereof are provided. These methods, compositions and kits find use in producing neurons, astrocytes, oligodendrocytes, and progenitor cells thereof for transplantation, for experimental evaluation, as a source of lineage- and cell-specific products, and the like, for example for use in treating human disorders of the CNS. Also provided are methods, compositions and kits for screening candidate agents for activity in converting cells into neuronal cells, astrocytes, oligodendrocytes, and progenitor cells thereof.

Abstract: Methods, compositions and kits for producing functional neurons, astroctyes, oligodendrocytes and progenitor cells thereof are provided. These methods, compositions and kits find use in producing neurons, astrocytes, oligodendrocytes, and progenitor cells thereof for transplantation, for experimental evaluation, as a source of lineage- and cell-specific products, and the like, for example for use in treating human disorders of the CNS. Also provided are methods, compositions and kits for screening candidate agents for activity in converting cells into neuronal cells, astrocytes, oligodendrocytes, and progenitor cells thereof.

Abstract: Methods, compositions and kits for producing functional neurons, astroctyes, oligodendrocytes and progenitor cells thereof are provided. These methods, compositions and kits find use in producing neurons, astrocytes, oligodendrocytes, and progenitor cells thereof for transplantation, for experimental evaluation, as a source of lineage- and cell-specific products, and the like, for example for use in treating human disorders of the CNS. Also provided are methods, compositions and kits for screening candidate agents for activity in converting cells into neuronal cells, astrocytes, oligodendrocytes, and progenitor cells thereof.

Abstract: Methods, compositions and kits for producing functional neurons, astroctyes, oligodendrocytes and progenitor cells thereof are provided. These methods, compositions and kits find use in producing neurons, astrocytes, oligodendrocytes, and progenitor cells thereof for transplantation, for experimental evaluation, as a source of lineage- and cell-specific products, and the like, for example for use in treating human disorders of the CNS. Also provided are methods, compositions and kits for screening candidate agents for activity in converting cells into neuronal cells, astrocytes, oligodendrocytes, and progenitor cells thereof.

Abstract: The present invention relates to in vitro and in vivo assays for the identification of agents that are useful in the treatment of neurodegenerative diseases that are associated with defects in protein folding. The present further relates to in vitro and in vivo assays for the identification of agents that contribute to the neurodegenerative processes which occur in these diseases. The present invention also relates to in vitro and in vivo models of neurodegenerative diseases. These assays and models will be useful in further understanding the pathogenesis of various neurodegenerative diseases in which defects in protein folding have been implicated, in identifying additional endogenous or environmental factors that contribute to the etiologies of these diseases, and in developing effective therapies for the prevention and/or treatment of these diseases.

Abstract: The present invention is directed to isolated nucleic acids encoding Mint protein variants having enhanced abilities to modulate the transcriptional activation mediated by the cytoplasmic tail of the amyloid precursor protein (APP) relative to wild-type Mint proteins. The present invention is further directed toward purified Mint protein variants having enhanced abilities to modulate the transcriptional activation mediated by the cytoplasmic tail of APP relative to wild-type Mint proteins. The present invention also encompasses methods of modulating transcriptional activation and methods of identifying compounds that modulate transcriptional activation, and vectors, as well as transfected cells and kits useful for modulating transcriptional activation or for the identification of compounds that can modulate transcriptional activation. The present invention further encompasses transgenic knockout mice with little or no expression of Mint 1, Mint 2 or Mint 3 proteins.

Abstract: The present invention is directed to isolated nucleic acids encoding Mint protein variants having enhanced abilities to modulate the transcriptional activation mediated by the cytoplasmic tail of the amyloid precursor protein (APP) relative to wild-type Mint proteins. The present invention is further directed toward purified Mint protein variants having enhanced abilities to modulate the transcriptional activation mediated by the cytoplasmic tail of APP relative to wild-type Mint proteins. The present invention also encompasses methods of modulating transcriptional activation and methods of identifying compounds that modulate transcriptional activation, and vectors, as well as transfected cells and kits useful for modulating transcriptional activation or for the identification of compounds that can modulate transcriptional activation. The present invention further encompasses transgenic knockout mice with little or no expression of Mint 1, Mint 2 or Mint 3 proteins.

Abstract: The present invention provides a composition comprising an isolated F-spondin polypeptide specifically bound to an APP or APLP polypeptide. The present invention further provides a composition comprising an isolated neurexin polypeptide specifically bound to an APP or APLP polypeptide. Also provided are methods of screening for modulators of the binding of an APP or an APLP polypeptide by F-spondin or neurexin proteins. Modulators of the binding of an APP or an APLP polypeptide by F-spondin or neurexin proteins may be useful in the treatment or prevention of AD.

Abstract: The present invention relates to in vitro and in vivo assays for the identification of agents that are useful in the treatment of neurodegenerative diseases that are associated with defects in protein folding. The present further relates to in vitro and in vivo assays for the identification of agents that contribute to the neurodegenerative processes which occur in these diseases. The present invention also relates to in vitro and in vivo models of neurodegenerative diseases. These assays and models will be useful in further understanding the pathogenesis of various neurodegenerative diseases in which defects in protein folding have been implicated, in identifying additional endogenous or environmental factors that contribute to the etiologies of these diseases, and in developing effective therapies for the prevention and/or treatment of these diseases.

Abstract: The present invention provides methods of identifying agents that affect the cleavage of amyloid-&bgr; precursor protein (APP) and related vectors, cells and kits, as well as agents identified by the method.

Abstract: The present invention provides methods of identifying agents that affect the cleavage of amyloid-&bgr; precursor protein (APP) and related vectors, cells and kits, as well as agents identified by the method.

Abstract: The present invention provides methods of identifying agents that affect the cleavage of amyloid-&bgr; precursor protein (APP) and related vectors, cells and kits, as well as agents identified by the method.

Abstract: The present invention is directed to isolated nucleic acids encoding Mint protein variants having enhanced abilities to modulate the transcriptional activation mediated by the cytoplasmic tail of the amyloid precursor protein (APP) relative to wild-type Mint proteins. The present invention is further directed toward purified Mint protein variants having enhanced abilities to modulate the transcriptional activation mediated by the cytoplasmic tail of APP relative to wild-type Mint proteins. The present invention also encompasses methods of modulating transcriptional activation and methods of identifying compounds that modulate transcriptional activation, and vectors, as well as transfected cells and kits useful for modulating transcriptional activation or for the identification of compounds that can modulate transcriptional activation. The present invention further encompasses transgenic knockout mice with little or no expression of Mint 1, Mint 2 or Mint 3 proteins.

Abstract: The present invention provides methods of identifying agents that affect the cleavage of amyloid-&bgr; precursor protein (APP) and related vectors, cells and kits, as well as agents identified by the method.

Abstract: Disclosed are discreet functionally translocatable DNA segments, termed Sterol Regulatory Elements (SRE's) , which are fused to heterologous structural genes to provide sterol regulatory capability to the thus formed hybrid gene. The hybrid genes respond to sterols by decreasing the production of messenger RNA. The SRE segments contain as their primary functional nucleotide sequence, a 16 bp sequence referred to as direct repeats 2, isolated from the 5' regions of the human LDL receptor gene. DNA segments which include this 16 nucleotide long sequence similarly confer sterol regulatory capability to previously known promoters such as the HSV TK promoter. Also disclosed are discreet sequences which confer positive transcription promotion to heterologous structural genes and promoters without conferring sterol responsivity. Methods are disclosed for employing these genetic control elements in a myriad of embodiments which provide for a fine-tune control of heterologous genes.

Abstract: Disclosed are discrete functionally translocatable DNA segments, termed Sterol Regulatory Elements (SREs), which are fused to heterologous structural genes to provide sterol regulatory capability to the thus formed hybrid gene. The hybrid genes respond to sterols by decreasing the production of messenger RNA. The SRE segments contain as their primary functional nucleotide sequence, a 16 bp sequence referred to as direct repeat 2, isolated from the 5' regions of the human LDL receptor gene. DNA segments which include this 16 nucleotide long sequence similarly confer sterol regulatory capability to previously known promoters such as the HSV TK promoter. Also disclosed are discrete sequences which confer positive transcription promotion to heterologous structural genes and promoters without conferring sterol responsivity. Methods are disclosed for employing these genetic control elements in a myriad of embodiments which provide for a fine-tune control of heterologous genes.