| abstract |
Chimeric neurotrophic factors comprising at least part of a natural cellular factor and part of at least one other molecule so that the chimeric molecule obtained exhibits neurotrophic activity. The invention is based, in part, on the discovery that chimeric molecules comprising parts of both nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are capable of possessing neurotrophic activity, and in some cases they have a spectrum of activity greater than that of the parent molecules. The invention is also based on the discovery that chimeric molecules comprising sequences of neurotrophic factors as well as additional peptide sequences can retain neurotrophic activity, and in some cases they can exhibit more potent activity than the parent factor. The chimeric neurotrophic factor molecules of the invention have a number of advantages over natural neurotrophic factors. Chimeric neurotrophic factors can be used to obtain, for example, the activity of two neurotrophic factors in a single molecule where they can serve as superagonists of an endogenous neurotrophic factor, thereby achieving an increased biological response to lower doses. |