Staurosporine, a streptomyces alkaloid toxin as a neurotropic tool

Staurosporine, a fungal kinase inhibitor, at non-toxic concentrations, induces neurite outgrowth in pheochromocytoma, PC12 cells, thus mimicking nerve growth factor (NGF) neurotropic effects. Characterization of staurosporine's neurotropic effects revealed rapid induction of short neurites which do not form complex neural networks, in contrast to NGF induced neurites. Staurosporine does not bind to NGF receptor, nor does it activate NGF high affinity receptors-"trk"tyrosine kinase. Furthermore, it's neurotropic effects are independent of protein kinase C inhibition. Staurosporine induced neurites rapidly acquire colchicine resistance and do not retract upon colchicine exposure. This colchicine resistance, induced by short term exposures to staurosporine, is correlated with increase in Tau-microtubule associated proteins levels. Further pharmacological characterization of staurosporine's neurotropic effects would pave the way for the development of the first generation of neurotropic drugs with clinical potentials.