ENZYME-DEFICIENT C3 BOTULINUM PROTEIN SPECIES AND THEIR USE TO PROMOTE NEURONAL GROWTH AND NEURONAL REGENERATION

摘要

The present invention is directed to nucleotide sequences and their encodedenzyme-deficient proteins and peptides which regulate neurite especiallyaxonal growth, recognitions agents thereto, and the therapeutic and diagnosticuses of such proteins and peptides. The invention relates also to the use ofenzyme-deficient or enzymatic inactive C3 proteins/peptide-derivatives derivedfrom Clostridium botulinum for regulation of the growth, expansion and/ordifferentiation of neurons and neuronal stem cells as well as the regenerationof neurons. In a specific embodiment of the invention, proteins and peptidesmay be used to promote the regeneration of neuronal axons over long distancesfollowing spinal cord damage. The proteins and peptides allow neuriteespecially axonal outgrowth - without actions on glial cells - in nervoussystem tissue in vivo and in vitro. They may have important uses in thetreatment of central nervous system damage and degenerative nerve diseases.