Senescence of the central nervous system is characterized by a progressive loss of neurons that can result in physiological and behavioral impairments. Reduction in the levels of central
neurotrophic factors or of
neurotrophin receptors may be one of the causes of the onset of these degenerative events. Thus, a proper therapeutic approach would be to increase support to degenerating neurons with trophic factors or to stimulate endogenous neurotrophic activity. Here we report that
acetyl-L-carnitine arginine amide (ST-857) is able to stimulate neurite outgrowth in rat
pheochromocytoma PC12 cells in a manner similar to that elicited by
nerve growth factor (
NGF). Neurite induction by
ST-857 requires de novo
mRNA synthesis and is independent of the action of several common trophic factors. The integrity of the molecular structure of
ST-857 is essential for its activity, as the single moieties of the molecule have no effect on PC12 cells, whether they are tested separately or together. Also, minor chemical modifications of
ST-857, such as the presence of the
arginine moiety at a position other than the amino one, completely abolish its neuritogenic effect. Lastly, the presence of
ST-857 in the culture medium competes with the high affinity
NGF binding in a dose dependent fashion. These results, although preliminary, are suggestive of a possible role for
ST-857 in the development of therapeutic strategies to counteract degenerative diseases of the CNS.