Neurotrophic roles of the beta-thymosins in the development and regeneration of the nervous system.

Beta-thymosins (Tbetas) are polypeptides abundant in the cytosol, nucleus, and extracellular space of many cell types. In the nervous system, the expression of Tbetas is regulated during the development of the central nervous system and following neuronal insults in cell-type and brain-region dependent manners, which may be related to the function of Tbetas in the growth and regeneration of the nervous system. Supporting such a proposition, overexpression of Tbetas in neurons has been shown to modify the axonal branches in vivo and neurite branches in vitro. These neurite-modifying functions have been suggested to be due to the activity of Tbetas to bind actin. In addition, we recently observed that Tbetas suppressed the apoptotic neuronal death in chick embryos, and these functions might be mediated by the extracellularly secreted form(s) of Tbetas. These results suggest that Tbetas play neurotrophic roles in the neuroprotection and neuronal growth/regeneration via their cytosolic actin-remodeling activity and extracellular antiapoptotic activity. Even though further verification is required, we also observed that Tbeta15 was translocated into the injured neuronal nuclei, and this event appeared to be an eliminatory process of the injured cells. Therefore, treatment with Tbetas or their related peptides appear to be beneficial for neuronal diseases by preventing neuronal death or promoting neuronal regeneration.