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

Abstract

Beta-thymosins (T beta s) are polypeptides abundant in the cytosol, nucleus, and extracellular space of many cell types. In the nervous system, the expression of T beta s 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 T beta s in the growth and regeneration of the nervous system. Supporting such a proposition, overexpression of T beta s 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 T beta s to bind actin. In addition, we recently observed that T beta s suppressed the apoptotic neuronal death in chick embryos, and these functions might be mediated by the extracellularly secreted form(s) of T beta s. These results suggest that T beta s 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 T beta 15 was translocated into the injured neuronal nuclei, and this event appeared to be an eliminatory process of the injured cells. Therefore, treatment with T beta s or their related peptides appear to be beneficial for neuronal diseases by preventing neuronal death or promoting neuronal regeneration.