Abstract: Methods for modulating the hypocretin system, as well as methods for identifying compounds that act as hypocretin-system modulators are provided. In modulating the hypocretin system, the method comprises administering a therapeutically effective amount of a preprohypocretin-expression modulator to an individual, wherein the preprohypocretin-expression modulator alters preprohypocretin expression in preprohypocretin-expressing cells. The method for identifying compounds comprises contacting a test compound to cells equipped with the 5′ flanking promoter of the preprohypocretin gene operably linked to a nucleic acid sequence and determining whether the test compound alters transcription of the nucleic acid sequence in the cell, wherein the test compound's ability to alter transcription is indicative of a compound that modulates the hypocretin system.

Abstract: Disclosed are hypocretin polynucleotides and hypocretin polypeplides, as well as antibodies, oligonucleotides, diagnostic kits and methods, and therapeutic compositions and methods. Hypocretin, one of several novel liypothalamic-specific polypeptides identified isolated and sequenced, is localized to regions of the hypothalamus involved in appetite and feeding behavior. Hypocretin polypeptides are biologically active, producing electrical changes in neurons, lowering body temperature and reducing food intake.

Abstract: Peptides and polypeptides found in the hypothalamus region of the mammalian brain are described, particularly hypocretin polypeptides and their uses. Hypocretin polypeptides are biologically active and produce electrical changes in neurons, lower body temperature, and reduce food intake.

Abstract: Methods for modulating the hypocretin system, as well as methods for identifying compounds that act as hypocretin-system modulators are provided. In modulating the hypocretin system, the method comprises administering a therapeutically effective amount of a preprohypocretin-expression modulator to an individual, wherein the preprohypocretin-expression modulator alters preprohypocretin expression in preprohypocretin-expressing cells. The method for identifying compounds comprises contacting a test compound to cells equipped with the 5′ flanking promoter of the preprohypocretin gene operably linked to a nucleic acid sequence and determining whether the test compound alters transcription of the nucleic acid sequence in the cell, wherein the test compound's ability to alter transcription is indicative of a compound that modulates the hypocretin system.