Abstract: In general, the invention provides methods, reagents, and uses for modulating cell survival. In various alternative aspects, the invention provides methods of modulating cell survival by administering a huntingtin protein or a biologically-active fragment or variant thereof, or methods of treatment or prophylaxis of a cell degenerative disease or a cell proliferative disease by administering a huntingtin protein or a biologically-active fragment or variant thereof. In various alternative aspects, the invention provides diagnostic assays or methods of assaying test compounds using a huntingtin protein or a biologically-active fragment or variant thereof.

Abstract: The present invention provides a means of modulating cell survival by modulating wild-type huntingtin protein function by administration of wild-type huntingtin protein, biologically active fragments thereof and/or antagonists of wild-type huntingtin. Accordingly, the present invention also provides biologically active fragments of wild-type huntingtin, antagonists of wild-type huntingtin and nucleic acid sequences encoding the biologically active fragments and peptide antagonists, and their use to modulate cell survival. In particular, the invention provides for means to activate or attenuate cell death within tissue, in order to facilitate the treatment of conditions where there is a dysregulation of cell death or cellular proliferation. Therapeutic application of this invention pertains to diseases and disorders including, but not limited to, Huntington disease, neurodegenerative diseases, stroke, and cancer.