The present invention is directed to nucleotide sequences and their encoded enzyme-deficient proteins and peptides which regulate neurite especially axonal growth, recognitions agents thereto, and the therapeutic and diagnostic uses of such proteins and peptides. The invention relates also to the use of enzyme-deficient or enzymatic inactive C3 proteins/peptide-derivatives derived from Clostridium botulinum for regulation of the growth, expansion and/or differentiation of neurons and neuronal stem cells as well as the regeneration of neurons. In a specific embodiment of the invention, proteins and peptides may be used to promote the regeneration of neuronal axons over long distances following spinal cord damage. The proteins and peptides allow neurite especially axonal outgrowth--without actions on glial cells--in nervous system tissue in vivo and in vitro. They may have important uses in the treatment of central nervous system damage and degenerative nerve diseases.