Vanderbilt University

Emory University

Duke University

Other

Florida Atlantic University

Randy D Blakely

Marc G Caron

Robert T Fremeau, Jr

Sandra J Rosenthal

David Miller

Ian D Tomlinson

Richard Nass

John N Mason

Cecil Mark Eppler

Shawn Patrick Ferguson

Erika M Adkins

Subramaniam Apparsundaram

Joel W Schwartz

Louis DeFelice

David Robertson

Maureen K Hahn

Loren Keith Henry

Based on the discovery that MBLAC1 is a specific, high-affinity target for Ceftriaxone (Cef), MBLAC1 may be used for identifying treatments for addiction to substances of abuse. Methods for identifying therapeutic agents for treatment of addiction to a substance of abuse include using an assay to determine if a test agent is capable of binding to MBLAC1 or disrupting binding between MBLAC1 protein and Cef, and identifying such a test agent as a candidate therapeutic agent for treatment of addiction to a substance of abuse. MBLAC knock-out (KO) animals, methods of use thereof, and kits are used for identifying a therapeutic agent that reduces the actions of at least one substance of abuse. Methods also include using cellular extracts from tissue or cultured cells taken from wild-type (WT) MBLAC1 and MBLAC1 KO animals for screening for novel, Cef-like molecules in vitro, and using cells from a MBLAC1 KO animal to test for Cef-like actions of a test molecule.

Methods for identifying treatments that reduce the actions of substances of abuse and addiction

The invention is based on the finding that IDT307 and analogs thereof are fluorescent substrates transported by several neurotransmitter transporters. Provided are methods for the analysis of neurotransmitter transport and binding using IDT307 and its analogs. The invention also provides rapid methods for screening for modulators of neurotransmitter transport.

Fluorescent substrates for neurotransmitter transporters

Provided are in vivo screening methods to detect and identify substances that affect neuronal viability, and/or prevent neurodegeneration, and/or confer neuroprotective effects The screening methods utilize recombinantexpressing a detectable marker in neuronal sub-groups and the use of neurotoxins specific to specific neuronal cells. Also provided are methods for identifying modulators of neurotransmitter transporters such as the dopamine transporter. Therefore, the invention provides methods for identifying substances that can be used in the prevention and therapy of neurodegenerative diseases.

[object Object]

The serotonin transporter (SERT) is a target of various therapeutic agents used in the treatment of neurological and neurodegenerative disorders. The present invention provides novel forms of SERT that lacks high affinity recognition of specific serotonin reuptake inhibitors (SSRIs). The present invention therefore provides a novel target for use in screening and model development that can aid both the discovery of new medications and the discovery of novel pathways impacted in parallel with SERT blockade. Such novel targets can help identify new SSRI's with unique modifications and lead to discovery of pathways that secondarily support the therapeutic activity of these agents.

Assays for novel serotonin transporter (SERT) blockers

Human high affinity choline transporter (CHT) cDNA was cloned from spinal cord and the primary structure and chromosomal localization have been determined. Mouse high affinity CHT cDNA was also cloned and characterized. An isolated polynucleotide, an isolated polypeptide, a recombinant host cell, a recombinant vector, a purified protein, an antibody, a nucleic acid detection kit, a method for screening cholinergic therapeutics, a method of treating a patient, a method of gene therapy and transgenic CHT mice are discussed.

Polynucleotide encoding a mouse choline transporter

The invention describes the finding that 4-(4-dimethylaminostyrl)-N-methylpyridinium or ASPis a fluorescent substrate that is transported by several neurotransmitter transporters. Provided are methods for the analysis of neurotransmitter transport and binding using ASP. The invention also provides rapid methods for screening for modulators of neurotransmitter transport. As neurotransmitter transporter defects are associated with numerous neurological disorders, the invention also provides methods for treating neurotransmitter transport-associated defects/conditions using the modulators identified by the screening methods of the invention.

Rapid assays for neurotransmitter transporters

Isolated polynucleotide molecules and peptides encoded by these molecules are used in the analysis of human norepinephrine (NE) transporter variants, as well as in diagnostic and therapeutic applications, relating to a human NE transporter polymorphism. By analyzing genomic DNA or amplified genomic DNA, or amplified cDNA derived from mRNA, it is possible to type a human NE transporter with regard to the human NE transporter polymorphism, for example, in the context of diagnosing and treating NE transport impairments, and disorders associated with NE transport impairments, such as orthostatic intolerance.

Genetic mutation underlying orthostatic intolerance and diagnostic and therapeutic methods relating thereto

Provided are in vivo screening methods to detect and identify substances that affect neuronal viability, and/or prevent neurodegeneration, and/or confer neuroprotective effects. The screening methods utilize recombinantexpressing a detectable marker in neuronal sub-groups and the use of neurotoxins specific to specific neuronal cells. Also provided are methods for identifying modulators of neurotransmitter transporters such as the dopamine transporter. Therefore, the invention provides methods for identifying substances that can be used in the prevention and therapy of neurodegenerative diseases.

Assay for toxin induced neuronal degeneration and viability in C. elegans

A nematode dopamine tansporter cDNA has been cloned, sequenced, and expressed, and provides a convenient screening assay for antiparasitics, as well as psychoactive drugs.

Nucleic acid encoding Nematode dopamine transporter and the protein encoded thereby

The anatomical distribution, nucleic acid sequence, pharmacological properties, and inferred structural features of a cDNA encoding a high affinity, Na.sup.+ -dependent rat brain L-proline transporter is described. The expression of this carrier in subpopulations of putative glutamatergic pathways supports a specific role for L-proline in excitatory amino acid neurotransmission. The cloned transporter cDNA predicts a 637 amino acid protein with 12 putative transmembrane domains and exhibits 44%-45% amino acid sequence identity with other neurotransmitter transporters. These findings support a synaptic role for L-proline in specific excitatory pathways in the CNS. The sequence can be used for expression of the transporter molecule, to make probes for the same protein from other species and related proteins, in diagnostic assays, and to design functional and structural analogs for use in research and possible clinical treatments. The protein is useful in making antibodies, conducting research studies, and design of therapeutic transporter modulators for clinical treatments.

High affinity L-proline transporter polypeptides; antibodies and

High affinity, brain-specific nucleic acids encoding a L-proline

Isolated DNA encoding a serotonin transporter is disclosed. Also disclosed are vectors and host cells containing the aforesaid DNA, methods of using the same, purified protein by the same, and oligonucleotides and antibodies which bind thereto. Specific embodiments are cDNAs encoding rat and human serotonin transporter.

Growing community of inventors

Brentwood, TN, United States of America

Randy D Blakely