Neuroprotective function of thymosin-beta and its derivative peptides on the programmed cell death of chick and rat neurons.

Thymosin-betas (Tbetas) are small polypeptides with various biological functions, including cytoskeletal remodeling, angiogenesis, cellular migration, wound healing, and regulation of apoptosis. Recently, we found that Tbeta is involved in the control of programmed cell death (PCD) of motoneurons (MNs) in chick embryo, and that the anti-apoptotic action of Tbeta is independent of its actin-sequestering activity. In this study, we observed that a synthetic peptide derived from Tbeta suppressed staurosporine-induced neuronal apoptosis in vitro, and PCD of chick or rat MNs in vivo. Furthermore, inhibition of Tbeta4 in chick embryo by antibody significantly augmented the PCD of MNs, suggesting that secreted form of Tbeta is physiological regulator of PCD. Based on these findings, we propose that extracellularly secreted Tbeta is involved in the control of PCD of neurons during development, and Tbeta-derived peptides could be useful for the anti-apoptotic therapy of neuropathologies related to neuronal apoptosis.